The number of genome projects has increased as technological improvements continue to lower the cost of sequencing.  (A)  Exponential growth of genome sequence databases since 1995.  (B)  The cost in US Dollars (USD) to sequence one million bases.  (C)  The cost in USD to sequence a 3,000 Mb (human-sized) genome on a log-transformed scale.


General schema showing the relationships of the  genome ,  transcriptome ,  proteome , and  metabolome  ( lipidome )


Overview of a genome project. First, the genome must be selected, which involves several factors including cost and relevance. Second, the sequence is generated and assembled at a given sequencing center (such as  BGI  or  DOE JGI ). Third, the genome sequence is annotated at several levels: DNA, protein, gene pathways, or comparatively.


An ABI PRISM 3100 Genetic Analyzer. Such capillary sequencers automated early large-scale genome sequencing efforts.


Illumina Genome Analyzer II System. Illumina technologies have set the standard for high-throughput massively parallel sequencing. [ 50 ]


An example of a protein structure determined by the Midwest Center for Structural Genomics


Environmental Shotgun Sequencing (ESS) is a key technique in metagenomics. (A) Sampling from habitat; (B) filtering particles, typically by size; (C) Lysis and DNA extraction; (D) cloning and library construction; (E) sequencing the clones; (F) sequence assembly into contigs and scaffolds.


Schematic  karyogram  of a human, providing a simplified overview of the human genome. It is a graphical representation of the idealized human  diploid  karyotype, with annotated  bands and sub-bands . It shows dark and white regions on  G banding . Each row is vertically aligned at  centromere  level. It shows 22  homologous   autosomal  chromosome pairs, both the female (XX) and male (XY) versions of the two  sex chromosomes , as well as the  mitochondrial genome  (at bottom left).  Further information:  Karyotype


The  DFT -method for identifying protein-coding segments of DNA


Evolution of the cost of sequencing a human genome from 2001 to 2021


Fluorophosphonate - rhodamine  (FP-Rhodamine) activity-based probe for profiling of the  serine hydrolase  superfamily.  In this probe the fluorophosphonate is the reactive group (RG) as it binds irreversibly to the active-site  serine   nucleophile  of  serine hydrolases  and the tag is  rhodamine , a fluorophore for in- gel  visualization.


In- gel  ABPP using probes with different fluorophores in the same lane to simultaneously profile differences in enzyme activities


Transcription units (in green) and genes (protein-coding genes in red, other genes in blue) of human adenovirus E genome


Allen Institute for Brain Science


Log-log plot  of the total number of annotated proteins in genomes submitted to  GenBank   as a function of genome size. Based on data from  NCBI  genome reports.


The BAM format; image from:  https://samtools.github.io/hts-specs/SAMv1.pdf


Hundreds of gel drops are visible on the biochip.


Figure 1. Biochips are a platform that require, in addition to microarray technology, transduction and signal processing technologies to output the results of sensing experiments.


3D  Sarfus  image of a DNA biochip


Chemogenomics  Staubli  robot retrieves assay plates from incubators


ChIP-exo workflow


Whole genome  alignment  is a typical method in comparative genomics. This alignment of eight  Yersinia  bacteria genomes reveals 78 locally collinear blocks  conserved  among all eight  taxa . Each chromosome has been laid out horizontally and  homologous  blocks in each genome are shown as identically colored regions linked across genomes. Regions that are  inverted  relative to  Y. pestis  KIM are shifted below a genome's center axis. [ 1 ]


Human  FOXP2  gene and evolutionary conservation is shown in and multiple alignment (at bottom of figure) in this image from the  UCSC Genome Browser . Note that conservation tends to cluster around coding regions (exons).


Phylogenetic tree of descendant species and reconstructed ancestors. The branch color represents breakpoint rates in RACFs (breakpoints per million years). Black branches represent nondetermined breakpoint rates. Tip colors depict assembly contiguity: black, scaffold-level genome assembly; green, chromosome-level genome assembly; yellow, chromosome-scale scaffold-level genome assembly. Numbers next to species names indicate diploid chromosome number (if known). [ 46 ]


Chromosome by chromosome variation of indicine and taurine cattle. The genomic structural differences on chromosome X between indicine ( Bos indicus  –   Nelore cattle ) and taurine cattle ( Bos taurus  –  Hereford cattle ) were identified using the SyRI tool.


Example of a phylogenetic tree created from an alignment of 250 unique spike protein sequences from the Betacoronavirus family.


Example of synteny block and break. Genes located on chromosomes of two species are denoted in letters. Each gene is associated with a number representing the species they belong to (species 1 or 2). Orthologous genes are connected by dashed lines and genes without an orthologous relationship are treated as gaps in synteny programs. [ 57 ]


Image from the study Evolution of the ancestral mammalian karyotype and syntenic regions. It is a Visualization of the evolutionary history of reconstructed mammalian chromosomes based on the human lineage. [ 46 ]


TCR  loci from humans (H, top) and mice (M, bottom) are compared, with TCR elements in red, non-TCR genes in purple, and V segments in orange, other TCR elements in red. M6A, a putative  methyltransferase ; ZNF, a  zinc-finger protein ; OR,  olfactory receptor  genes; DAD1, defender against  cell death ; The sites of species-specific, processed pseudogenes are shown by gray triangles. See also  GenBank  accession numbers AE000658-62. Modified after Glusman et al. 2001. [ 81 ]


[Figure 2] Gene structure of the human (top) and mouse (bottom) V, D, J, and C gene segments. The arrows represent the transcriptional direction of each TCR gene. The squares and circles represent going in a direct and reverse direction. Modified after Glusman et al. 2001. [ 81 ]


Overlapping reads from paired-end sequencing form contigs; contigs and gaps of known length form scaffolds.


This  gene duplication  has created a copy number variation. The chromosome now has two copies of this section of DNA, rather than one.


Diagrammatic representation of non-allelic homologous recombination. Here, Gene X represents the gene of interest and the black line represents the chromosome. When the two homologous chromosomes are misaligned and recombination occurs, it may result in a duplication of the gene.


Timeline of the change in hominin diet throughout late Paleolithic, Mesolithic, and Neolithic periods. As seen, root vegetables rich in starch were consumed around 20,000 years ago when the  AMY1  diploid gene number is estimated to have increased.


Simplified phylogenetic tree of the great ape lineage and the number of diploid  AMY1  genes that each species has.  AMY1  gene number shown to increase after split with the chimpanzee lineage.


Possible mechanism of how multiple copies of a gene can lead to a protein family over years with natural selection. Here, Gene X is the gene of interest that is duplicated and Gene X1 and Gene X2 are genes that acquired mutations and became functionally different to Gene X.


Metabolic reconstruction of a member of the Delphibacteria phylum. [ 1 ]  Key predicted metabolic and functional features are depicted. Genes of interest are denoted by abbreviations in the colored shapes. Filled shapes represent genes predicted to be present or likely to be present, whereas unfilled shapes represent genes that were not identified.


A, B: Two genomes with four synteny blocks. C: The adjacency graph of the genomes pictured in A and B.


Duplex sequencing overview:  Duplex tagged libraries containing sequencing adapters are amplified and result in two types of products each originates from a single strand of DNA. After sequencing the PCR products, the generated reads divide into tag families based on the genomic position, duplex tags, and the neighboring sequencing adapter. Sequence tag α is the reverse complement of sequence tag β and vice versa.


Duplex sequencing library preparation workflow:  Two adapter oligos go through several steps (Annealing, Synthesis, dT-tailing) to generate double-stranded unique tags with 3'-dT-overhangs. Then the duplex tag adapters ligate to the double-stranded DNA templates. Finally, Illumina sequencing adapters are inserted into the tagged-DNA fragments and form the final libraries containing DS adapters, Illumina sequencing adapters, and template DNA.


Essential genes in  Mycobacterium tuberculosis  H37Rv as found by using  transposons  which insert in random positions in the genome. If no transposons are found in a gene, the gene is most likely essential as it cannot tolerate any insertion. In this example, essential  heme biosynthetic genes   hemA, hemB, hemC, hemD  are devoid of insertions. The number of sequence reads (‘‘reads/TA’’) is shown for the indicated region of the H37Rv chromosome. Potential TA dinucleotide insertions sites are indicated. Image from Griffin et al. 2011. [ 16 ]


A schematic view of essential genes (or proteins) in  lysine biosynthesis  of different  bacteria . The same protein may be essential in one species but not another.


Conservation of essential genes in  bacteria , adapted from  [ 72 ]


Deep mutational scan of the RNA recognition motif (RRM2) of a yeast PolyA binding protein (Pab1)


A  DNA microarray


Overview of Perturb-seq workflow


An example of a CRISPR loss-of-function screen [ 14 ]


An overview of a phydms workflow


Samples used and eQTLs discovered in GTEx v6


This workflow figures describes the sequential steps for performing G&T-seq: Cell sorting and lysis, separation of mRNA and gDNA, genome and transcriptom amplification, and sequencing and analysis.


The process of mRNA isolation and amplification of cDNA


Schematic overview of the modular structure underlying procedures for gene set enrichment analysis


An image of the 46 chromosomes making up the diploid genome of a human male (the mitochondrial chromosomes are not shown).


Part of DNA sequence – prototypification of complete genome of virus


In a typical human cell, the genome is contained in 22 pairs of  autosomes , two  sex chromosomes  (the female and male variants shown at bottom right), as well as the  mitochondrial genome  (shown to scale as "MT" at bottom left).  Further information:  Karyotype


Log–log plot  of the total number of annotated proteins in genomes submitted to  GenBank  as a function of genome size


Comparison among genome sizes


This heatmap displays the similarity between nuclear profiles using cells that take on values from 0 - 1


This bar graph shows how the radial positions of nuclear profiles are distributed across a cluster


This is a radar chart that represents 3 cluster's presence in different features of the mouse genome


Flowchart


An example of a proximity matrix produced with GAMtools.


How genomic compaction and radial position affect detection frequency


flowchart showing a general process of GAM data analysis.  Circles represent a process and squares represent data.


Flow chart of SLICE


Heatmap for 81 window by 81 window matrix


An example of conversion between cosegregation and linkage matrices. Note the red highlighted cells, illustrating edges that may be missed if the mean cosegregation is not normalized.


An example of calculating degree centrality from a simple graph and adjacency matrix.


An evolutionary tree of mammals. [ 3 ]


Examples of mammalian chromosomes. [ 5 ]


Examples of the distribution of C-heterochromatin in mammalian chromosomes. [ 11 ]


A comparative chromosome map of birds' and mammals' inferred human homologies (right numbers) on chromosome  idiograms [ 29 ]


Circular representation of the  Mycobacterium leprae  genome created using JCVI online genome tools.


The principal forces of evolution in prokaryotes and their effects on  archaeal  and  bacterial  genomes. The horizontal line shows archaeal and bacterial genome size on a  logarithmic scale  (in mega base pairs ) and the approximate corresponding number of genes (in parentheses).The effects of the main forces of prokaryotic genome evolution are denoted by triangles that are positioned, roughly, over the ranges of genome size for which the corresponding effects are thought to be most pronounced.


Chromosome fusion, leading to a reduced number of chromosomes (here a fused  human chromosome 2 , with 2 separate chromosomes still present in  chimpanzees  and other  apes ).


The proS loci in  Mycobacterium leprae  and  M. tuberculosis , showing 3 pseudogenes (indicated by crosses) in  M. leprae  that still represent functional genes in  M. tuberculosis . Homologous genes are indicated by identical colors and vertical, hatched bars. Modified after Cole et al. 2001. [ 28 ]


Cichlids such as  Tropheops tropheops  from  Lake Malawi  provide models for genome evolution.


Genome size ranges (in base pairs) of various life forms


Schematic  karyogram  of a human. It shows 22  homologous chromosomes , both the female (XX) and male (XY) versions of the  sex chromosome  (bottom right), as well as the  mitochondrial genome  (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA  base pairs . Further information:  Karyotype


Genome skimming allows for assembly of high-copy fractions of the genome into contiguous, complete genomes.


The black-chinned hummingbird ( Archilochus alexandri ) is the bird species known to have the smallest genome among birds, which is only 0.91 Gb long.


Introns are DNA sequences that occur in eukaryotic genes. They are transcribed to mRNA, but they are edited out before the mRNA is translated by ribosomes.


The genus name of the sparrows,  Passer , gives its name to the order of  Passeriformes . Birds classified in this order have the highest rate of point mutations among birds, though birds generally have lower rates than mammals.


Genome sizes and corresponding composition of six major model organisms as pie charts. The increase in  genome  size correlates with the vast expansion of noncoding (i.e., intronic, intergenic, and interspersed repeat sequences) and repeat  DNA  (e.g., satellite, LINEs,  short interspersed nuclear element  (SINEs), DNA ( Alu sequence ), in red) sequences in more complex multicellular organisms. This expansion is accompanied by an increase in the number of  epigenetic  mechanisms (particularly repressive) that regulate the genome. Expansion of the genome also correlates with an increase in size and complexity of transcription units, except for plants. P =  Promoter  DNA element.


An example of a  phylogenetic tree  with its different phylostrata. Considering the large grey bars as the phylogeny of the taxa and the thin coloured lines as the various gene lineages within them, we can deduce the presence of two founder genes 1 and 2 present in their respective phylostrata 1 and 2. The phylostrata will then be usually given the name of the smallest determinable clade including all taxa present. [ 1 ]


Distinct microbial communities in sponges converge to have common functionality despite retaining phylogenetic differences. [ 10 ]


TSC SNP distribution along the long arm of chromosome 22 (from  https://web.archive.org/web/20130903043223/http://snp.cshl.org/  ). Each column represents a 1 Mb interval; the approximate cytogenetic position is given on the x-axis. Clear peaks and troughs of SNP density can be seen, possibly reflecting different rates of mutation, recombination and selection.


Populations with a high level of parental-relatedness result in a larger number of homozygous gene knockouts as compared to outbred populations. [ 98 ]


A pedigree displaying a first-cousin mating (carriers both carrying heterozygous knockouts mating as marked by double line) leading to offspring possessing a homozygous gene knockout


Shared sequences and structural variants between genomes in  Human Pangenome Reference


A brief overview of different steps in genome de novo assembly


Currently available application and tools for Human Pangenome Reference [ 12 ]


CSIR-IGIB South Campus


Workflow overview of a MALBAC experiment.


Detection of drug resistance genes using MALBAC


Metabolic network  showing interactions between enzymes and metabolites in the  Arabidopsis thaliana  citric acid cycle. Enzymes and metabolites are the red dots and interactions between them are the lines.


Metabolic network model for  Escherichia coli


This is a visual representation of the metabolic network reconstruction process.


In metagenomics, the genetic materials ( DNA ,  C ) are  extracted  directly from samples taken from the environment (e.g. soil, sea water, human gut,  A ) after filtering ( B ), and are  sequenced  ( E ) after multiplication by  cloning  ( D ) in an approach called  shotgun sequencing . These short sequences can then be put together again using  assembly methods  ( F ) to deduce the individual genomes or parts of genomes that constitute the original environmental sample. This information can then be used to study the  species diversity  and functional potential of the microbial community of the environment. [ 1 ]


Flow diagram of a typical metagenome project [ 19 ]


Schematic representation of the main steps necessary for the analysis of whole metagenome shotgun sequencing-derived data. [ 27 ]  The software related to each step is shown in italics.


Metagenomics allows the study of microbial communities like those present in this stream receiving acid drainage from surface coal mining.


Workflow overview of the MeDIP procedure. MeDIP procedure is followed by array-hybridization (A) or high-throughput/next generation sequencing (B)


Simple workflow demonstrating a typical experiment using MeDIP-seq.


The MinCDE system. MinD-ATP binds to a cell pole, also binds MinC, which prevents the formation of FtsZ polymers. The MinE ring causes hydrolysis of MinD's bound ATP, turning it into ADP and releasing the complex from the membrane. The system oscillates as each pole builds up a concentration of inhibitor that is periodically dismantled.


MinD (cyan) chased by MinE (magenta) to form spiraling waves on an artificial membrane


Gene functions in  Syn 3.0 , a minimal-genome variant of  Mycoplasma genitalium


Pelagibacter ubique , the ubiquitous free-living ocean bacterium with the smallest (~1100) number of genes


Mammalian mitochondria under an electron microscope


Two  Nanoarchaeum equitans  cells (and its larger host  Ignicoccus )


Capsid of the Bacteriophage MS2 capsid (capsule), entirely composed of one protein. Colored by quasi-equivalent conformational variant (a,b,c).


Comprehenseive whole-cell model of Mycoplasma genitalium


Genome mining is associated with bioinformatics investigations.


The A-DNA double helix molecular model of Crick and Watson (consistent with X-ray data) for which they, with M.H.F. Wilkins, received a Nobel Prize.


Silica  glass is another example of a material which is organized into a paracrystalline lattice.


Molecular models are useful in the  design  of structures for  DNA nanotechnology . Here, individual DNA tiles (model at left) self-assemble into a highly ordered DNA 2D-nanogrid ( AFM  image at right).


Diagram illustrating genomics


"Omicum": Building of the  Estonian Biocentre  which houses the  Estonian Genome Centre  and Institute of Molecular and Cell Biology at the  University of Tartu  in Tartu,  Estonia .


A  National Oceanic and Atmospheric Administration  scientist using microbiomics to study marine ecosystems


Pangenome analysis of  Streptococcus agalactiae  genomes made with Anvi'o  [ 1 ]  software whose development is led by  A. Murat Eren . Genomes obtained from Tettelin et al. (2005). [ 2 ]  Each circle corresponds to one genome and each radius represent a gene family. At the bottom and at right are localized the core genome families. Some families in the core may have more than one homologous gene per genome. In the middle, at the left of the figure the shell genome is observed. At the top left are shown families from the dispensable genome and singletons.


In the pangenome, we can identify three sets of genes: Core, Shell, and Cloud genome. The Core genome comprises the genes that are present in all genomes analyzed. To avoid dismissing families due to sequencing artifacts some authors consider the softcore (>95% occurrence). The Shell genome consists of the genes shared by the majority of genomes (10-95% occurrence). The gene families present in only one genome or <10% occurrence are described as Dispensable or Cloud genome.


a) Closed pangenomes are characterized by large core genomes and small accessory genomes. b) Open pangenomes tend to have small core genomes and large accessory genomes. c) The size of open pangenomes tends to increase with every added genome, meanwhile closed pangenome's size tends to be asymptotic despite adding more genomes. Due to this characteristic, complete pangenome size for closed pangenomes can be predicted.


The supergenome is defined as all genes accessible for a certain species, the pangenome if sequencing of all genomes of one species was available. Metapangenome is the pangenome analysis applied to metagenomic samples, where the union of genes of several species is evaluated for a given habitat.


The  S. pneumoniae  pan-genome. (a) Number of new genes as a function of the number of sequenced genomes. The predicted number of new  genes  drops sharply to zero when the number of genomes exceeds 50. (b) Number of core genes as a function of the number of sequenced genomes. The number of core genes converges to 1,647 for number of genomes n→∞. From Donati et al. [ 36 ]


Pangenome analysis of genomes of  Streptococcus agalactiae . [ 2 ]  Example of phylogenies made with BPGA software. This software allows us to generate phylogenies based on the clustering of the core genome or pangenome. Core and pan phylogenetic reconstructions are not necessarily matching.


Pangenome graph of 3 117  Acinetobacter baumannii  genomes generated with PPanGGOLiN software. Edges correspond to genomic colocalization and nodes correspond to genes. The thickness of the edges is proportional to the number of genomes sharing that link. The edges between persistent (similar to core genes), shell and cloud nodes are colored in orange, green and blue, respectively.


Example of possible outputs of BPGA software. Pangenome analysis of genomes of  Streptococcus agalactiae . At the left, the distribution of Go terms by core/dispensable/unique genome is shown. In this example, the category replication, recombination, and repair are enriched on unique gene families. On the right, a typical pan/core plot is shown, when more genomes have added the size of the core is decreasing, and on the contrary the size of the pangenome increases. [ 2 ]


pgEd Logo


Typical cost of sequencing a human-sized genome, on a logarithmic scale. Note the drastic trend faster than  Moore's law  beginning in January 2008 as  post-Sanger sequencing  came online at sequencing centers. [ 10 ]


Overview of Perturb-seq workflow


Final consensus terms for allele functional status and phenotype


Consecutive phases and associated challenges in Pharmacogenomics. [ 48 ]


Objectives as a hierarchy for predictive genomics.


Proteogenomics uses an integrated approach by combining  genomics ,  proteomics , and  transcriptomics .


Image of a eukaryote cell illustrating how proteins are made: DNA in the nucleus is read by RNA polymerase, then ribosomes in the cytoplasm produce an amino acid strand that folds into a functional protein.


Robotic preparation of  MALDI   mass spectrometry  samples on a sample carrier


LCQ Mass Spectrometer used in mass spectrometry.


Mechanisms showing how AHA labels onto proteins and where biotin-FLAG-alkyne tags mark the amino acid. Hand Drawn via Sigma Aldrich


Ketone and aldehyde mechanism with cell surface labeling. Staudinger ligations and their interaction with azide groups for labeling are shown in the second figure.


An outline of the protocol for reduced representation bisulfite sequencing


Reduced Representation Bisulfite Sequencing Protocol


The first printout of the human reference genome presented as a series of books, displayed at the  Wellcome Collection , London


Diagram of reads arrangement, forming  contigs  and these can be assembled into  scaffolds  in the complete process of sequencing and assembly of a reference genome. The gap between contig 1 and 2 is indicated as sequenced, forming a scaffold, while the other gap is not sequenced and separates scaffold 1 and 2.


Evolution of the cost of sequencing a human genome from 2001 to 2021


Chromosomes ideogram of the human reference genome assembly GRCh38/hg38. Characteristic bands patterns are displayed in black, grey and white, while the gaps and partially assembled regions are displayed in blue and rose, respectively. Reference: Genome Data Viewer of the NCBI. [ 24 ]


An overview of methods for single-cell epigenomic sequencing. Each method is labelled on the bottom row. Arrows are coloured by method, showing the flow from starting material to sequence data. Adapted from  [ 1 ]


One method for single cell DNA methylation sequencing [ 4 ]


Comparison of single cell DNA methylation sequencing methods in terms of coverage as at 2015 on  Mus musculus


Two methods for single-cell ATAC-seq [ 8 ]


SMRT Cell for a RS or RS II Sequencer


SMRT Cell for a Sequel Sequencer


Pipette tip in an 8M SMRT Cell


Genomic regions of the identified  S. meliloti  sRNA genes. The schematics (drawn to scale) summarize the bioinformatic predictions and the results of the experimental mapping. The smr genes are represented by red arrows and the flanking ORFs by blue arrows. Numbers indicate co-ordinates in the  S. meliloti  1021 genome database. Experimentally determined 5'- and 3'-ends of the Smr transcripts are indicated with numbers. 3'-ends of the differentially expressed sRNAs were assigned to the last U in the consecutive stretch after extended stem-loops of Rho-independent terminators, which are denoted by green dots above the horizontal lines. The grey arrowhead indicates the processing site for Smr7C.


Directed graph of relationships among SNP prediction webservers and their bioinformatics sources. [ 2 ]


Different type of annotations in genomics


An animated example to show the utility of a spaced seed. First, an attempt to identify a local candidate match without a space seed is made (unsuccessfully), before attempting the same task with a simple spaced seed, where a hit is found successfully. Green indicates a matching base position. See  here  for more details.


Transcription, splicing and translation of a eukaryotic gene.  A eukaryotic gene consists of a promoter, exons, introns and a poly-A addition site. It is transcribed into a primary RNA transcript (or pre-mRNA) by the RNA polymerase enzyme. This RNA undergoes the process of editing by the spliceosome for the precise removal of the introns and joining of the exons, which produces the mRNA molecule. This mRNA contains the complete coding sequence without any interrupting stop codons that is translated by the ribosome into the protein encoded by the gene. In the figure, the lengths of introns are short, but in reality, they are extremely long, on average 20 times longer than the exons, and often even much longer up to around 500,000 bases. The exons are usually short with an average of ~120 bases, and with an upper maximum of ~600 bases. [ 1 ]  Also shown is an example protein structure ( PDB ID: 2VUX ) for the Human ribonucleotide reductase, subunit M2 B.


The clustering of stop codons in a random DNA sequence lead to rare ORFs that are long.  The negative exponential frequency distribution of the ORF lengths in a random sequence indicates that, in a linear sequence, the shorter the ORFs they are more frequent, and the longer the ORFs they are less and less frequent. Thus, there is a tendency for stop codons to be clustered in most places in a sequence, and, therefore, the longer ORFs are rarer, even within the upper maximum length of ~600 bases. Senapathy reasoned that, coding sequence segments from the available long ORFs could be chosen as exons, whereas the intervening sequences with clusters of stop codons could be earmarked as introns to be deleted from the primary RNA transcript, which would lead to a split gene structure.


The negative exponential distribution of ORF lengths in a random DNA sequence and in eukaryotic DNA sequences.  Senapathy found that stop codons occur at a high frequency in a random DNA sequence, as 3 stop codons exist out of 64 codons, which leads to short open reading frames (ORFs) with average length of ~60 bases. He also found that the lengths of the ORFs are distributed in a negative exponential manner. This plot indicates that the frequency of the zero ORF length (consecutive stop-codons occurring tandemly) is the most frequent of all ORF lengths, the frequency of ORF length of one codon (3 bases) is the next most frequent, and so on. The frequency of longer ORFs reduces exponentially, and reaches a zero frequency around an ORF length of ~600 bases, which means that ORFs longer than 600 bases do not occur. [ 1 ]  Surprisingly, the plot from the eukaryotic DNA sequences was almost exactly the same as that from the random DNA sequences.


Corroboration of the Split Gene Theory by actual DNA sequences of human genes.  The Split Gene Theory predicts that all three stop codons should be present at a high frequency in each of the three reading frames (RFs), which would lead to short Open Reading Frames (ORFs). It also predicts that: a) exons would occur within these short ORFs in all three RFs; b) introns would be long, and that c) exon lengths would be confined to ORF lengths. These predictions are precisely true in the DNA sequences of most eukaryotic genes. Two example genes ( FLJ35894  and  ADCY1 ) from the human genome are shown. All of the exons in each gene are short, and most of the introns are long. In each gene, the exons (short yellow boxes) are confined to short ORFs that occurred in the DNA sequence. In addition, stop codons occur at the ends of the exons, which are actually part of the splice junction sequences.


Origin of splice junction sequences from the stop codons. [ 1 ] [ 2 ] [ 3 ]  (A) The molecular machinery that chose the exons of a split gene from a random primordial DNA sequence should be capable of searching for stop codons (tick marks) to identify regions without stop codons (in the primary RNA copy, not shown), which are the ORFs. In doing so, the first encountered stop codon will be marked as the start of the intron. This process will lead to the presence of a stop codon at the beginning of the introns. Sometimes, all of an Open Reading Frame is chosen to be an exon, because of which the end of the previous intron will have a stop codon. (B) The start and the end of the intron are parts of the "splice junction sequences," that signal the exact point of splicing to the spliceosome machinery. The stop codons are shown with a red background.


Stop codons occur as key parts of all important genetic elements in eukaryotic genes.  The key genetic elements of eukaryotic genes are the promoters, donor and acceptor splice junction signals, lariat (branch point) signals, and poly-A addition sites. The core component of each of these genetic elements is a stop codon.


Origin of bacterial genes from split genes.  The split genes of modern eukaryotes with short exons (average length of 120 bases, and maximum of ~600 bases) interrupted by long introns are extremely probable in random DNA sequences due to the reasons described in the section  Origin of introns and the split gene structure , above. In contrast, the long contiguously coding bacterial genes (that can be as long and 10,000 bases, and longer up to 90,000 bases) without introns are practically impossible to occur in random sequences. Thus, the only way that bacterial genes could originate was to delete the introns from the split genes that occurred in random DNA sequences and produce contiguously coding genes. The example protein shown with its 3D structure is from PDB database ( ID:1UNF ).


Short tandem repeat (STR) analysis on a simplified model using  polymerase chain reaction  (PCR): First, a DNA sample undergoes PCR with  primers  targeting certain STRs (which vary in lengths between individuals and their  alleles ). The resultant fragments are separated by size (such as  electrophoresis ). [ 1 ]


A partial human STR profile obtained using the  Applied Biosystems  Identifiler kit


An example of a protein structure from  Protein Data Bank .


Subfunctionalization is a neutral mutation process in which each paralog retains a subset of its original ancestral function. The figure illustrates that the ancestral gene (orange & blue) is capable of both functions before gene duplication. After gene duplication the functional capabilities are divided amongst the gene copies. After this divergence each paralog is capable of independently performing a distinct ancestral function.


Within a family, linkage occurs when two genetic markers (points on a chromosome) remain linked on a chromosome rather than being broken apart by recombination events during meiosis, shown as red lines. In a population, contiguous stretches of founder chromosomes from the initial generation are sequentially reduced in size by recombination events. Over time, a pair of markers or points on a chromosome in the population move from linkage disequilibrium to linkage equilibrium, as recombination events eventually occur between every possible point on the chromosome. [ 1 ]


LD plot of SNPs with top-ranked bayes factors in CHB of 1000 Genome Phase I. The colors indicate the strength of pairwise LD according to r2 metrics. The SNPs marked with asterisks represent independent strong associations. Tag SNPs are shadowed in pink. [ 7 ]


Two Affymetrix chips


Global aquaculture production of  Takifugu rubripes  in thousand tonnes from 1980 to 2022, as reported by the  FAO [ 3 ]


DNA microarray  used to analyze the expression of human (left) and mouse genes.


Proposed clinical trial paradigm for discovery of toxgnostics markers through GWAS.


The translatome is characterized using polysome profiling, ribosome footprinting, TRAP-seq, RNC-seq, and other translatomics techniques. Created in BioRender.com.


The image depicts a conceptual diagram of transmembrane protein 217. The protein is given from N-terminus to C-terminus with predicted cellular, transmembrane and extracellular domains present (colored blue, grey, and orange respectively). The most highly conserved predicted post-translational modifications are provided as well. The following predicted post-translational modifications are provided: phosphorylation sites, disulfide bond, and a C-linked mannosylation.


Three examples of the triangle inequality for triangles with sides of lengths  x ,  y ,  z . The top example shows a case where  z  is much less than the sum  x  +  y  of the other two sides,  and the bottom example shows a case where the side  z  is only slightly less than  x  +  y .


General Timeline of Human Genome Project


Brief work flow of whole exome sequencing; DNA double strands are first digested in to single strands. Coding area (exon) and non-coding area (intron) are differentiated, and linear DNA are fragmented into the genomic DNA. Hybridization on capture array for target (coding area) enrichment. Finally, assayed by DNA sequencing program.


Patients with cancer such as breast cancer, lung cancer or prostate cancer recruited to be analyzed by genomic sequencing. They will be separated into different groups depending on their genetic information, and different types of medications will be distributed to the subgroups.


Decreasing trend in cost of genome sequencing


Electropherograms  are commonly used to sequence portions of genomes. [ 1 ]


Schematic  karyogram  of a human, showing an overview of the  human genome , with 22  homologous chromosomes , both the female (XX) and male (XY) versions of the  sex chromosome  (bottom right), as well as the  mitochondrial genome  (to scale at bottom left)


The first bacterial whole genome to be sequenced was of the bacterium  Haemophilus influenzae .


The worm  Caenorhabditis elegans  was the first animal to have its whole genome sequenced.


Drosophila melanogaster 's  whole genome was sequenced in 2000.


Arabidopsis thaliana  was the first plant genome sequenced.


The genome of the lab mouse  Mus musculus  was published in 2002.


It took 10 years and 50 scientists spanning the globe to sequence the genome of  Elaeis guineensis  ( oil palm ). This genome was particularly difficult to sequence because it had many  repeated sequences  which are difficult to organise. [ 8 ]


An ABI PRISM 3100 genetic analyzer. Such capillary sequencers automated the early efforts of sequencing genomes.


Total cost of sequencing a whole human genome as calculated by the  NHGRI


An amplicon sequence template that has been prepared for amplification. The target sequence to be amplified is colored green.


Cross-linked DNA extracted from the 4,000-year-old liver of the ancient Egyptian priest Nekht-Ankh


Quagga (Equus quagga quagga), an extinct sub-species of zebra.


A diptera (Mycetophilidae) from the Eocene (40-50 million years ago) in a piece of transparent Baltic amber along with other smaller inclusions. Shown under daylight (big photograph) and under UV light (small photograph).


Svante Pääbo (left) with his medal for the Nobel Prize on Physiology or Medicine.


Map of human fossils with an age of at least ~40,000 years that yielded genome-wide data [ 77 ]


Left: Unbound aptamer. Right: the aptamer bound to its target protein. The protein is in yellow. Parts of the aptamer that change shape when it binds its target are in blue, while the unchanging parts are in orange. The parts of the aptamer that contact the protein are highlighted in red.


Breast cancer  cells incubated with aptamers that bind selectively to  biomarkers  on the cancer cells, but not to healthy cells. Aptamers are linked to  Alexa Fluor 594 , a molecule that glows red under  UV  light. This type of test allows a doctor or researcher to identify cancer cells in a  tissue sample from a patient .


Jack Szostak, Nobel laureate and one of the inventors of SELEX and aptamers.


The complex and diverse secondary and tertiary structure of aptamers, as shown in this schematic of an aptamer's secondary structure, is what lets them bind their target strongly and specifically.  Complementary base pairing  is visible in the black lines connecting some G-C and A-T bases. This is a feature of nucleic acids that does not exist in the amino acids of antibodies. It helps aptamers form these unique structures. Hairpin regions (red), which rely on this base pairing, enhance the aptamer's stability at different temperatures. This image also shows examples of chemical modifications to the base aptamer. Two unnatural bases, which enhance durability, are in yellow. The  biotin  molecule binds with extreme strength to  streptavidin , allowing the aptamer to be anchored to other molecules or to a surface in sensors and assays.


This assay tests the ability of two different types of aptamers (V and I) to detect their respective protein targets (VEGF and IFN-y). The labels Apt1, Apt2, Apt3, and Apt4 are in decreasing order of binding strength (i.e. Apt1 is the strongest aptamer). The DD, AD, DA, and AA letters mean that they have different combinations of unnatural base pairs. This causes their difference in binding strengths. The "-" columns have no protein, and the "+" columns do have protein. Aptamer with protein (+) and without protein (-) is loaded into wells in a gel and moves down the column lanes. If target is present, they bind and travel more slowly, due to the  charge  on the aptamer and the mass of the protein. Otherwise, the unbound aptamer moves quickly to the end of the lane. The difference in position between the "+" and "-" bands is the "mobility shift." This allows the researcher to detect the presence or absence of the protein. The darker band in the leftmost V and I lanes show that stronger aptamer-target binding makes it easier to detect the target at a given amount of target protein in the sample. The bottom image includes  denaturing   urea  in the gel that disrupts aptamer-target binding in the weaker I aptamers, showing that the aptamer-protein binding is indeed what caused the mobility shift.


BBF RFC 10 assembly of two BioBricks compatible part. Treating the upstream fragment with EcoRI and SpeI, and the downstream fragment with EcoRI and XbaI allows for the assembly in the desired sequence. Because SpeI and XbaI produce complementary overhangs, they help link the two DNA fragments together, producing a scar sequence. All the original restriction sites are maintained in the final construct, which can then be used for further BioBricks reactions.


The sequence of DNA parts for the Golden Gate assembly can be directed by defining unique complementary overhangs for each part. Thus, to assemble gene 1 in order of fragment A, B and C, the 3' overhang for fragment A is complementary to the 5' overhang for fragment B, and similarly for fragment B and fragment C. For the destination plasmid, the selectable marker is flanked by outward-cutting BsaI restriction sites. This excises the selectable marker, allowing the insertion of the final construct. T4 ligase is used to ligate the fragments together and to the destination plasmid.


Long-overlap-based assembly methods require the presence of long overlap regions on the DNA parts that are to be assembled. This enables the construction of complementary overhangs that can anneal via complementary base pairing. There exist a variety of methods, e.g. Gibson assembly, CPEC, MODAL that make use of this concept to assemble DNA.


The MODAL standard provides a common format to allow any DNA part to be made compatible with Gibson assembly or other overlap assembly methods. The DNA fragment of interest undergoes two rounds of PCR, first to attach the adaptor prefix and suffixes, and next to attach the predefined linker sequences. Once the parts are in the required format, assembly methods like Gibson assembly can carried out. The order of the parts is directed by the linkers, i.e. the same linker sequence is attached to the 3' end of the upstream part and the 5' end of the downstream part.


The second AT-hook of  HMGA1  (black ribbon) bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden.


The phosphate backbone of the DNA shown in orange is faded to focus on the central region of the AT-hook. Shown in magenta are the side chains Pro35, Arg36, Gly37, Arg38, and Pro39. Made with PyMol. PDB code: 3UXW.


There are multiple hydrogen bonds shown in yellow. The interactions occur between Arg38 and Pro39 (3.8 Å), Pro35 and Arg36 (2.5 Å), and Gly37 and Arg38 (2.4 Å). The red sphere represents a water that forms a hydrogen bond 2.7 Å from Arg38 with the bond shown in yellow. Made with PyMol. PDB code: 3UXW.


Synthetic Biology Open Language (SBOL) standard visual symbols for use with BioBricks Standard


Abstraction hierarchy allows the breakdown of complexity.


Standard assembly of two BioBrick parts (promoter and coding sequence) by digestion and ligation  which forms a "scar" site(M).


Biofusion assembly of two BioBrick parts.The schematic diagram shows the 6 base pair scar site made due to the deletion and insertion of nucleotide in the  XbaI  and  SpeI  sites.


An LB agar plate showing the result of a blue–white screen.


A schematic representation of the blue–white assay, used to screen for recombinant vectors


Cassette mutagenesis via  Golden Gate Assembly


A diagram of DNA base pairing, demonstrating the basis for Chargaff's rules


Histogram showing how 20309 chromosomes adhere to Chargaff's second parity rule


Chargaff's 2nd parity rule for prokaryotic 6-mers


Basic Principle of CLIP


HITS-CLIP [ 26 ] [ 27 ]


PAR-CLIP [ 26 ] [ 27 ]


iCLIP [ 26 ] [ 27 ]


CLIP Summary [ 26 ] [ 28 ] [ 27 ]


Figure 1. Steps of Terminal Restriction Fragment Length Polymorphism analysis for a single microbial community with 3 phylotypes


Figure 2. The microbial fingerprinting technique called Denaturing Gradient Gel Electrophoresis. The diagram demonstrates how samples from different microbial communities can be compared.


Figure 3. The microbial fingerprinting technique called (Automated) Ribosomal Intergenic Spacer Analysis. The diagram shows the output of both Automated RISA (Pathway 1) or RISA (Pathway 2).


Cartoon model of Cre recombinase bound to its substrate (DNA). The amino terminal domain is shown in blue whilst the carboxyl domain is green. (A side view)


Cartoon model of Cre recombinase bound to its substrate (DNA). The amino terminal domain is shown in blue whilst the carboxyl domain is green. (A head on view)


This cartoon model of Cre recombinase bound to its substrate (DNA) shows the amino acids involved in the active site in red and labelled. This image is generated following cleavage of the DNA.


A diagram describing how Lox71 and Lox66 sites can be used to combine two plasmids into one contiguous plasmid.


A model experiment in genetics using the Cre-lox system: the premature stop sequence present in floxed mice is removed only from cells that express Cre recombinase when the mice are bred together


Intrastrand and interstrand crosslinking of DNA


Chemical structure of a Nitrogen Mustard


Structure of DNA crosslink induced by Nitrogen Mustard.


Chemical structure of Cisplatin


Chemical structure of DNA crosslink induced by Cisplatin.


Chemical structure of BNCU, a carmustine derivative.


Chemical structure of DNA crosslink induced by a Carmustine.


Chemical structure of Mitomycin C.


Chemical structure of a DNA crosslink induced by Mitomycin C.


Chemical structure of Psoralen.


Chemical structure of DNA crosslink induced by Psoralen.


Chemical structure of malondialdehyde and derivatives.


Structure describing a DNA crosslink by a malondialdehyde.


Structure of two variants of DNA crosslinking induced by Oxidative Stress and/or UV radiation.


Chemical structure of Nitrous acid.


Chemical structure of DNA crosslink indiuced by Nitrous acid.


A  metabolite  of  benzo[ a ]pyrene  forms an  intercalated   DNA adduct , at center


Figure 2: Reactive Sites of Interest for Nucleic Acids in DNA Adduct Formation


Figure 3: DNA damaged by carcinogenic 2-aminofluorene


Figure 4: Effects of Tobacco on Healthy Human DNA


Principle of DamID. This sketch shows an idealized view of the DNA molecule wrapped around  histones  within the nucleus of a cell. The enzyme Dam (green) is fused to the protein of interest (orange) by expression of a chimeric DNA sequence. The protein of interest drags Dam onto its cognate targets. The tethering leads to methylation of GATCs in the neighborhood of the binding site (red) but not at a distance.


The image demonstrates how ligase (yellow oval) catalyzes two DNA fragment strands. The ligase joins the two fragments of DNA to form a longer strand of DNA by "pasting" them together.


A pictorial example of how a ligase works (with  sticky ends )


Hybridization of the target to the probe


The steps required in a microarray experiment


Two Affymetrix chips. A  match  is shown at bottom left for size comparison.


Diagram of typical dual-colour  microarray experiment


Examples of levels of application of microarrays.  Within the organisms, genes are transcribed and spliced to produce mature mRNA transcripts (red). The mRNA is extracted from the organism and reverse transcriptase is used to copy the mRNA into stable ds-cDNA (blue). In microarrays, the ds-cDNA is fragmented and fluorescently labelled (orange). The labelled fragments bind to an ordered array of complementary oligonucleotides, and  measurement of fluorescent intensity  across the array indicates the abundance of a predetermined set of sequences. These sequences are typically specifically chosen to report on genes of interest within the organism's genome. [ 18 ]


Gene expression values from microarray experiments can be represented as  heat maps  to visualize the result of data analysis.


National Center for Toxicological Research  scientist reviews microarray data.


DNA origami object from viral DNA visualized by  electron tomography . [ 1 ]  The map is at the top and atomic model of the DNA colored below. (Deposited in  EMDB   EMD-2210 )


The process of fabricating DNA Origami


A DNA Origami Dynamic Machine using a directional component and brownian motion to generate rotation.


A diagram of DNA origami being attached to antigens to generate Programmable T-cell Engagers.


A diagram of molecular self-assembly of DNA origami structures for nanotechnological applications.


Illumina Genome Analyzer II sequencing machine


Oxford Nanopore MinION sequencer (lower right) was used in the first-ever DNA sequencing in space in August 2016 by astronaut  Kathleen Rubins . [ 36 ]


Typical dot blot membrane. Darker dots indicate more protein.


Screenshot of a chromatogram inside the program " Sequencher "


Capillary Electrophoresis to Electropherogram process (Courtesy of www.biointeractive.org)


Generation of results


Close-up of DNA ladders on an agarose gel. GelRed stain was used.


Loading of a sample into a polyacrylamide gel electrophoresis well.


Chemical structure of Ethidium Bromide.


Chemical structure of SYBR Green I.


Chemical structure of Coomassie Brilliant Blue R-250


Lane 1 is a negative control, and contains only genetic material. Lane 2 contains protein as well as a DNA fragment that, based on its sequence, does not interact.  Lane 3 contains protein and a DNA fragment that does react; the resulting complex is larger, heavier, and slower-moving. The pattern shown in lane 3 is the one that would result if all the DNA were bound and no dissociation of complex occurred during electrophoresis.  When these conditions are not met  a second band might be seen in lane 3 reflecting the presence of free DNA or the  dissociation of the DNA-protein complex.


Schematic of an EMSA showing the labeled DNA (dark band) move up the gel as more protein is added, as indicted by the triangle below


3′ to 5′ Exonuclease associated with Pol I


WRN Exonuclease with active sites in yellow


A bacterial expression vector for expressing  green fluorescent protein  from the  T7 promoter .


An example of a bacterial expression vector is the pGEX-3x plasmid


This figure depicts how Floxing is used in scientific research for spatial and temporal control of gene expression.


A model experiment in genetics using the Cre-lox system: the premature stop sequence present in floxed mice is removed only from cells that express Cre recombinase when the mice are bred together.


Workflow for utilizing selection in a functional cloning experiment. Here only genes providing  ampicillin  resistance are selected.


Genomic library in  Saccharomyces cerevisiae  host.


Flow chart to decide on the optimum cloning strategy.


Artificial gene drive using a  CRISPR-Cas9  system: gRNA instructs Cas9 to cut at the rival allele, causing the repair mechanism to replace the damage with the Cas9-containing allele


Molecular mechanism of a gene drive based on Cas9 and guide RNA.


Heat maps  of gene expression values show how experimental conditions influenced production (expression) of mRNA for a set of genes. Green indicates reduced expression.  Cluster analysis  has placed a group of down regulated genes in the upper left corner.


Ingenuity Gene Network Diagram [ 22 ]  which dynamically assembles genes with known relationships. Green indicates reduced expression, red indicates increased expression. The algorithm has included unregulated genes, white, to improve connectivity.


A  chimeric  mouse gene targeted for the  agouti coat color gene , with its offspring


Wild-type  Physcomitrella  and  knockout mosses : Deviating phenotypes induced in gene-disruption library transformants.  Physcomitrella  wild-type and transformed plants were grown on minimal Knop medium to induce differentiation and development of  gametophores . For each plant, an overview (upper row, scale bar corresponds to 1 mm) and a close-up (bottom row, scale bar equals 0.5 mm) is shown. A, Haploid wild-type moss plant completely covered with leafy gametophores and close-up of wild-type leaf. B–E, Different mutants. [ 1 ]


A Venn Diagram to show the relationship between three types of 'Genetic engineering'; Genetic Modification, Gene Targeting and Genome Editing.


Possible DNA repair outcomes after cutting by  CRISPR , leading to gene editing. Both strands of DNA are cut by CRISPR-Cas (or other site-specific nuclease) to create a double-strand-break (DSB). The DSB is then repaired through two alternative DNA repair pathways ( NHEJ  or  HR ) to lead to random mutations at the cut site ("targeted mutagenesis") or specific mutations if a repair template is supplied that contains those specific edits ("gene targeting").


Shared DNA for different relatives


Map of human migration  out of Africa , according to Mitochondrial DNA. The numbers represent thousands of years before present time. The blue line represents the area covered in ice or tundra during the last great ice age. The North Pole is at the center. Africa, the center of the start of the migration, is at the top left and South America is at the far right.


Strand 1 differs from strand 2 at a single base pair location (a C → T polymorphism).


European genetic structure (based on Autosomal SNPs) by  PCA


SFP discovery principle for gene probing


Newborn heel-prick blood sample collection


Small amounts of the chorionic villi are sampled during CVS


Plants such as an infertile cotton strain have been made in laboratories using GURT. [ 1 ]


A GURT process that uses biological signals to make enzymes that cut out the blocker sequence.


A human neocortical  pyramidal neuron  stained via Golgi technique. Notice the apical dendrite extending vertically above the soma and the numerous basal dendrites radiating laterally from the base of the cell body. Photo by Bob Jacobs, Colorado College.


Drawing by Camillo Golgi of a  hippocampus  stained with the silver nitrate method


Drawing of a  Purkinje cell  in the  cerebellum   cortex  done by Santiago Ramón y Cajal, clearly demonstrating the power of Golgi's staining method to reveal fine detail


RNA  in situ  hybridization -  KRT5  and housekeeping gene in human  melanoma   FFPE  tissue section - visualized under brightfield and fluorescence microscope


Multiplex RNA visualization in cells using ViewRNA FISH Assays


In situ  hybridization of wild type  Drosophila  embryos at different developmental stages for the RNA from a gene called  hunchback .


Analysis of collagen expression in young Salamanders ( P. waltl ) via Hybridization Chain Reaction RNA Fluorescence  In Situ  Hybridization (HCR RNA-FISH) technology


Four main limiting factors leading to no initiation of replication in iterons


Representation of the molecular structure of protein RepA, a known rep protein used in iterons


Micrographic  karyogram of human male using  Giemsa  staining


Schematic  karyogram demonstrating the basic knowledge needed to read a karyotype


Chromosomes at various stages of  mitosis . Karyograms are generally made by chromosomes in prometaphase or metaphase. During these phases, the two copies of each chromosome (connected at the  centromere ) will look as one unless the image resolution is high enough to distinguish the two.


Micrograph of human chromosomes before further processing. Staining with Giemsa confers a purple color to chromosomes, but micrographs are often converted to  grayscale  to facilitate data presentation and make comparisons of results from different laboratories. [ 7 ]


Micrographic karyogram of a human male. See section text for details.


Schematic karyogram of a human. Even at low magnification, it gives an overview of the  human genome , with numbered chromosome pairs, its main changes during the  cell cycle  (top center), and the  mitochondrial genome  to scale (at bottom left). See section text for more details.


The  cell cycle


Karyogram from a human female  lymphocyte  probed for the  Alu sequence  using  FISH


Spectral karyogram of a human female


Spectral human karyotype


Fusion of ancestral chromosomes left distinctive remnants of telomeres, and a vestigial centromere


Bacteriophage Lambda Structure at Atomic Resolution [ 1 ]


Bacteriophage lambda virion (schematic). Protein names and their copy numbers in the virion particle are shown. The presence of the L and M proteins in the virion is still unclear. [ 5 ]


Linear layout of lambda phage genome with major operons, promoter regions and capsid coding genes. [ 5 ]


Lambda phage J protein interaction with the LamB porin


Lambda phage DNA injection into the cell membrane using Mannose PTS permease (a sugar transporting system) as a mechanism of entry into the cytoplasm


Early activation events involving N protein


Lysis plaques of lambda phage on  E. coli  bacteria


Diagram showing the retro-regulation process that yields a higher concentration of xis compared to int. The mRNA transcript is digested by bacterial RNase starting from the cleaved hairpin loop at sib.


A simplified representation of the integration/excision paradigm and the major genes involved.


Lysogen repressors and polymerase bound to OR1 and recruits OR2, which will activate PRM and shutdown PR.


Transcriptional state of the P RM  and P R  promoter regions during a lysogenic state vs induced, early lytic state.


The function of LexA in the SOS response.  LexA expression leads to inhibition of various genes including LexA.


Protein interactions that lead to either Lytic or Lysogenic cycles for Lambda phage


Visual representation of repressor tetramer/octamer binding to phage lambda L and R operator sites (stable lysogenic state)


Diagram of temperate phage life cycle, showing both lytic and lysogenic cycles.


Loop-mediated isothermal amplification (LAMP) process [ 1 ]


Loop-mediated isothermal amplification (LAMP) primers [ 1 ]


Loop-mediated isothermal amplification (LAMP) product [ 1 ]


Schema of a LAMP of nucleic acid biomarkers from raw untreated wastewater samples, to rapidly quantify human-specific mitochondrial DNA (mtDNA). [ 6 ]


Colorimetric  detections [ 13 ]


Human cheek cells stained with methylene blue


Methylene blue crystals


Gross pathology of a normal brain and a brain of a patient treated with methylene blue before death.


Absorption spectrum of methylene blue, in terms of the  molar extinction coefficient  (base 10 logarithm). In this dataset a peak  absorbance  of 1.7 (i.e. 98% of transmitted light absorbed) was observed with 665 nm light passing through 1 cm of 10 micromolar methylene blue solution.


Structure of molecular beacons in their native conformations (top) or hybridized with a DNA strand (bottom)


The structure of a typical molecular beacon probe


Diagram of molecular cloning using bacteria and plasmids


The overall goal of molecular cloning is to take a gene of interest from one plasmid and insert it into another plasmid. [ 9 ]  This is done by performing PCR, digestive reaction, ligation reaction, and transformation.


Diagram of a commonly used cloning plasmid;  pBR322 . It's a circular piece of DNA 4361 bases long. Two  antibiotic resistance   genes  are present, conferring resistance to  ampicillin  and  tetracycline , and an  origin of replication  that the host uses to  replicate  the DNA.


Cleavage of a DNA sequence containing the  BamHI   restriction site . The DNA is cleaved at the palindromic sequence to produce 'sticky ends'.


DNA for cloning is most commonly produced using  PCR . Template DNA is mixed with  bases  (the building blocks of DNA), primers (short pieces of complementary single stranded DNA) and a  DNA polymerase  enzyme that builds the DNA chain. The mix goes through cycles of heating and cooling to produce large quantities of copied DNA.


A molecular-weight size marker in the form of a 1 kb  DNA ladder in the rightmost lane, used in gel electrophoresis. Gel conditions are 1% agarose, 3  volt /cm, and  ethidium bromide  stain.


Electrophoresed gel with DNA ladders of varying lengths in left lane and middle lane. Fragments sizes are marked on the right, in  base pairs .


1.2% agarose gel showing two different DNA ladders dyed with  GelRed  stain


Immunoblot with protein ladder in leftmost lane. Fragment sizes are measured in kDa ( kilodaltons ).


Lane of electrophoresed agarose gel showing an RNA ladder with bands at a range of 281-6583 base pairs


SDS-PAGE gel using a molecular-weight size standard in the left outer lane


An electrophoresed gel showing PCR products. The leftmost lane represents a DNA ladder with fragments at 100bp intervals.


Segment of a Morpholino-RNA heteroduplex, 8-mer shown


Eukaryotic gene expression without intervention by a Morpholino


Translation blocked by a Morpholino oligo


Splicing blocked by a Morpholino oligo


A pUC19 cloning vector showing the multiple cloning site sequence with restriction enzyme sites.


A diagram showing the process of inserting a multiple cloning site into a plasmid vector.


Tandem (top) versus interspersed (bottom) repeated nucleic acid sequence


Labeling of cytidine.  Left: unlabeled cytidine, right: ribose-labeled cytidine (red dots =  13 C).


General workflow of NAIL-MS assays.  Cells are cultivated in the appropriately labeled medium before harvesting and RNA isolation. Further RNA purification is followed by digestion to nucleosides and subsequent triple quadrupole mass spectrometry.


Overview of the Global run on sequencing assay for delineating genes, genome-wide, that are engaged in transcription.


Rotavirus


Scheme. 1.  i :  N -Chlorosuccinimide; Bn = -CH 2 Ph


Scheme 2. Synthesis of oligonucleotides by the H-Phosphonate Method


Scheme. 3 Oligonucleotide coupling by phosphodiester method; Tr = -CPh 3


Scheme 4. Oligonucleotide coupling by phosphotriester method; MMT = -CPh 2 (4-MeOC 6 H 4 ).


Protected 2'-deoxynucleoside phosphoramidites.


2'- O -protected ribonucleoside phosphoramidites.


Non-nucleoside phosphoramidites for 5'-modification of synthetic oligonucleotides. MMT =  mono-methoxytrityl,(4-methoxyphenyl)diphenylmethyl.


Scheme 5. Synthesis cycle for preparation of oligonucleotides by phosphoramidite method.


Commercial solid supports for oligonucleotide synthesis.


Scheme 6. Mechanism of 3'-dephosphorylation of oligonucleotides assembled on universal solid supports.


S p  and R p -diastereomeric internucleosidic phosphorothioate linkages.


Commercial sulfur transfer agents for oligonucleotide synthesis.


5'- O -MeNPOC-protected nucleoside phosphoramidite.


Deconvoluted ES MS of crude oligonucleotide 5'-DMT-T 20  (calculated mass 6324.26 Da).


Example of DNA profiling in order to determine the father of a child (Ch). Child's DNA sample should contain a mixture of different size DNA bands of both parents. In this case, person #1 is likely the father.


Plasmid miniprep. 0.8%  agarose gel   ethidium bromide -stained.


An illustrated procedure for Polony sequencing


A microbiologist runs a pulsed-field gel electrophoresis test used in bacterial typing


Cluster analysis in  BioNumerics  of the enteroaggregative  Escherichia coli  strains from the pulsed-field gel electrophoresis fingerprinting


A Punnett square showing a typical  test cross . (green pod color is dominant over yellow for pea pods [ 1 ]  in contrast to pea seeds, where yellow  cotyledon  color is dominant over green [ 2 ] ).


Punnett squares for each combination of parents' colour vision status giving probabilities of their offsprings' status, each cell having 25% probability in theory.


There are also Punnett squares for  epistasis . In these cases the genotype epistatic over the other genes hinders their expression in the phenotype.


Construction of recombinant DNA, in which a foreign DNA fragment is inserted into a plasmid vector. In this example, the gene indicated by the white color is inactivated upon insertion of the foreign DNA fragment.


Figure 1: Principle of RMCE:  exchange of genetic cassettes (´flip´ step) is enabled by a  recombinase  (´Flp´) from yeast. Part B shows mutants (Fn) of the naturally occurring 48 bp  FRT -site (F). If a gene cassette is flanked by a set of these sites (F and Fn, for example) it can change places, by double-reciprocal recombination,  with a second cassette that is part of an exchange plasmid (Figure 1, part A). A model experiment is shown in part C, in which an ´empty´ cell is modified  by either a standard  transfection  approach or by RMCE. Please note that in the first case multiple genomic sites are hit, each giving raise to a different expression level (cf. the broad distribution of green dots). If a pre-defined genomic address is used to introduce the same gene reporter, each  clone  derived from such an event shows comparable expression characteristics


Figure 2: Multiplexing RMCE . In the given example a reporter gene cassette (gfp/tk/neo), flanked by four heterospecific  FRT- sites (F5/F3-F/Fn) is introduced into the genome. The unique F5/F3 address can then be used to introduce an upstream-regulatory element and the F/Fn address to apply a similar modification at the downstream end. after the expression of the gfp-reporter has been optimized by systematic changes of this type, the central reporter cassette can be exchanged for any ´gene-of-interest´(GOI): the GOI will be flanked by the F3 and F-sites, respectively and introduced accordingly while the flanking elements will remain in place


A diagram of a how a reporter gene is used to study a regulatory sequence.


RNP-MaP workflow overview


An overview of the major stages in the RNA Immunoprecipitation chip procedure.


Saturation mutagenesis of a single position in a theoretical 10-residue protein. The wild type version of the protein is shown at the top, with M representing the first amino acid methionine, and * representing the termination of translation. All 19 mutants at position 5 are shown below.


Depiction of one common way to clone a site-directed mutagenesis library (i.e., using degenerate oligos). The gene of interest is PCRed with oligos that contain a region that is perfectly complementary to the template (blue), and one that differs from the template by one or more nucleotides (red). Many such primers containing degeneracy in the non-complementary region are pooled into the same PCR, resulting in many different PCR products with different mutations in that region (individual mutants shown with different colors below).


Site saturation mutagenesis is a type of site-directed mutagenesis. This image shows the saturation mutagenesis of a single position in a theoretical 10-residue protein. The wild type version of the protein is shown at the top, with M representing the first amino acid methionine, and * representing the termination of translation. All 19 mutants of the isoleucine at position 5 are shown below.


Fig. 1. Tyr-Recombinases: Details of the crossover step. Top: Traditional view including strand-exchange followed by branch-migration (proofreading). The mechanism occurs in the framework of a synaptic complex (1) including both DNA sites in parallel orientation. While branch-migration explains the specific homology requirements and the reversibility of the process in a straightforward manner, it cannot be reconciled with the motions recombinase subunits have to undergo in three dimensions. Bottom: Current view. Two simultaneous strand-swaps, each depending on the complementarity of three successive bases at (or close to) the edges of the 8-bp spacer (dashed lines indicate base-pairing). Didactic complications arise from the fact that, in this model, the synaptic complex must accommodate both substrates in an anti-parallel orientation. This synaptic complex (1) arises from the association of two individual recombinase subunits ("protomers"; gray ovals) with the respective target site. Its formation depends on inter-protomer contacts and DNA bending, which in turn define the subunits (green) with an active role during the first crossover reaction. Both representations illustrate only one half of the respective pathway. These parts are separated by a Holliday junction/isomerization step before the product (3) can be released.


Fig. 2. Ser-Recombinases: The (essentially irreversible) subunit-rotation pathway. Contrary to Tyr-recombinases, the four participating DNA strands are cut in synchrony at points staggered by only 2 bp (leaving little room for proofreading). Subunit-rotation (180°) permits the exchange of strands while covalently linked to the protein partner. The intermediate exposure of double-strand breaks bears risks of triggering illegitimate recombination and thereby secondary reactions. Here, the synaptic complex arises from the association of pre-formed recombinase dimers with the respective target sites (CTD/NTD, C-/N-terminal domain). Like for Tyr-recombinases, each site contains two arms, each accommodating one protomer. As both arms are structured slightly differently, the subunits become conformationally tuned and thereby prepared for their respective role in the  recombination cycle. Contrary to members of the Tyr-class the recombination pathway converts two different substrate sites (attP and attB) to site-hybrids  (attL and attR) . This explains the irreversible nature of this particular recombination pathway, which can only be overcome by auxiliary "recombination directionality factors" (RDFs).


Fig. 3A. Reversible insertion and excision by the Cre-lox system.


Fig. 3B. Inversion by the Cre-lox system.


A set of hypothetical NGS reads are shown, aligned against a reference sequence. At the annotated locus, the reads contain a mixture of A/G nucleotides, against the A reference allele. Depending on the prior genotype probabilities, and the chosen error model, this may be called as a heterozygous SNV (genotype AG predicted), the G nucleotides may be classified as errors and no variant called (genotype AA predicted), or alternatively the A nucleotides may be classified as errors and a homozygous SNV called (genotype GG predicted).


A schematic of the major phases in a SELEX experiment. This cycle, may be repeated up to 20 times over a period lasting weeks, though some methods require far fewer cycles.


Structure of an RNA aptamer specific for  biotin . The aptamer surface and backbone are shown in yellow. Biotin (spheres) fits snugly into a cavity of the RNA surface.


Adenine (left) bonded to x-thymine (right).


Adenine (left) bonded to y-thymine (right).


Naphtho-homologated Adenine (xxA)


Congenital anomalies deaths per million persons in 2012:     0–26    27–34    35–46    47–72    73–91    92–111    112–134    135–155    156–176    177–396


Disability-adjusted life year  for congenital anomalies per 100,000 inhabitants in 2004: [ 103 ]      no data      less than 160      160–240      240–320      320–400      400–480      480–560      560–640      640–720      720–800      800–900      900–950      more than 950


The structure of 1q21.1; similar regions in the same color


Observed relation within 1q21.1


X-linked recessive inheritance.


Autosomal dominant inheritance


Mother and child with achondroplasia with unaffected father, showing inheritance


Detail of  Las Meninas  by  Diego Velázquez  (1656), showing Maribarbola and Nicolasito Pertusato (right), achondroplastic dwarfs in the entourage of  Infanta Margarita


Munchkin dwarf cat


Arachnoid cyst as seen on a CT image of the brain


Axial CT showing a typical arachnoid cyst left temporal


Protein TF (from TF gene)


Anemia


RBC


Figure 1. Pattern of cerebrospinal fluid markers in autosomal dominant GTP cyclohydrolase I deficiency compared with other forms of  tetrahydrobiopterin deficiency , from a consensus guideline by Thomas Opladen et al., 2020. [ 2 ]


Adjacent regions of cardiac tissue with differing refractory periods can lead to a normally smooth wavefront of depolarisation undergoing wavebreak leading to re-entrant arrhythmias


ECG pattern in Brugada syndrome. According to consensus guidelines, Type 1 ST segment elevation, either spontaneously present or induced with the sodium channel-blocker challenge test, is considered diagnostic. Type 2 and 3 may lead to suspicion, but provocation testing is required for diagnosis. The ECGs in the right and left panels are from the same patient before (right panel, type 3) and after (left panel, type 1) administration of Ajmaline.


Illustration of an implanted cardioverter-defibrillator


Example of a pedigree of Camptodactyly inheritance


Splint for the left little (pinky) finger of a 7-year-old child.


X-ray image of anal atresia in human infant


Antero-posterior radiographic view, showing missing ribs, absent lumbosacral vertebrae, hypoplastic pelvis and "frog-like" position of the lower extremities


In the egg of the  marbled newt  ( Triturus marmoratus ), the  neurula  phase begins


Proper development into a  larva , as observed in the  northern crested newt  ( Triturus cristatus )


In the cladogram by Wielstra and Arntzen, the  outgroup  is the genus  Calotriton  (above, the  Pyrenean brook salamander ,  C. asper ), in which the described developmental arrest does not occur


Group of male and female patients of various ages with CIDS


Disability-adjusted life years  (DALY) lost from iodine deficiency in 2012 in proportion to a million people       52–163      181–217      221–221      222–310      320–505      512–610      626–626      653–976      984–1,242      1,251–3,159


Cretinism ( Styria ), copper engraving, 1815


Infant with skin lesions from congenital rubella


"Salt-and-pepper" retinopathy is characteristic of congenital rubella. [ 6 ] [ 7 ]


Congenital rubella serology timeline


Amniotic band syndrome of the hand in a 26-year-old male


Infant with craniopagus parasiticus ("supernumerary head")


Drawing of the Boy of Bengal, affected by craniopagus parasiticus


A Swedish description from 1793 of a newborn with cyclopia


Cystic hygromas are classically found in the  posterior triangle  of the neck.


Newborn infant with a cystic hygroma visible on right side of the neck


A chick with two beaks and three eyes


Spanish case of diprosopus, born 1775


An example of a "Janus cat"


Patient with Duane syndrome attempting to look far right. Notice the affected left eye faces straight and up, rather than following the right eye to the right.


Individual with classical EDS displaying skin hyperelasticity.  Not all people with EDS have this trait.


The collagen fibril and EDS: (a) Normal collagen fibrils are of uniform size and spacing. Fibrils from a person with dermatosparaxis (b) show dramatic alterations in fibril morphology with severe effects on the tensile strength of connective tissues. A person with classical EDS (c) shows composite fibrils. Fibrils from a TNX-deficient person (d) are uniform in size and no composite fibrils are seen. TNX-null (e) fibrils are less densely packed and not as well aligned to neighboring fibrils.


Stevie Boebi and Annie Elainey, who have EDS, standing with mobility aids on the red carpet


Tessier classification. Left: boney clefts, Right: Soft tissue clefts.


Bilateral number 4 orbital clefts


Partial 3-11 orbital cleft


Facial characteristics of a child with FAS


A  label on alcoholic drinks  promoting zero alcohol during  pregnancy


Smooth philtrum seen on a six-month-old baby with FAS


Beer Street  and  Gin Lane , William Hogarth (1751)


Anteroposterior abdominal radiograph shows a soft-tissue mass in the right hemiabdomen. The mass contains calcified osseous-appearing structures of varying sizes and shapes.


The postoperative specimen from the previous image shows a fairly well developed fetus lying on its back, with rudimentary digits.


A  computed tomography  scan of the same patient's abdomen pre-operation reveals a large retroperitoneal soft-tissue mass. There are long hyperdense opacities that resemble fetal bones.


DNA sequencing electropherograms of a typical FOP patient being compared to other 2 patients. The unsure base "N" indicates site heterozygous for mutation and wild-type gene.


Syndactyly of the second and third toes.


The microcephaly condition.


The process of gene transcription and translation.


Box osteotomy for hypertelorism correction. Red box indicates the surgical site.


Severe Goldenhar syndrome in a 10-year-old girl


Limbal dermoid  as seen in Goldenhar syndrome


This condition can be inherited in an  autosomal dominant  manner.


Tognina's parents, Petrus and Catherine, by Hoefnagel . National Gallery of Art Washington


Petrus, Tognina's father.


Hajdu–Cheney syndrome has an  autosomal dominant  pattern of  inheritance . The above example is demonstrated in the case of a carrier parent.


Autosomal recessive inheritance


This condition is inherited in an autosomal dominant manner. [ 1 ]


Micrograph  showing a duodenal biopsy with gastric heterotopia;  H&E stain


Ubiquitin protein


Smith–Lemli–Opitz syndrome(or 7-dehydrocholesterol reductase deficiency)


Cobb angle measurement of a dextroscoliosis


An  autosomal dominant  pattern


The setup for BPAP using a mechanical ventilator


Diagram of a neonatal heart affected by PDA


Malpuech facial clefting syndrome has an autosomal recessive pattern of inheritance.


The short and long arm of a typical human chromosome.


Hair in Marinesco–Sjögren syndrome, showing lack of pigment and medulla


Monstrous births and  omens  in the  Nuremberg Chronicle .


A two-headed cow.


Sixteenth-century oil painting,  Painting of a handicapped man .


Mentally disabled woman with features indicative of Muenke syndrome


Muenke Syndrome is inherited in an  autosomal dominant  pattern.


Chr 17


Growth hormone


Cytogenetic location of the POMGnT 1 gene is 1p34.1. [ 14 ]


A brain MRI showing lissencephaly (smooth brain) with ventriculomegaly.


The distal, or terminal phalanges ( orange ) are at the end of the fingers and toes.


Schematic of the human X chromosome


Nasodigitoacoustic syndrome has an X-linked recessive pattern of inheritance.


Babygram  of stillborn baby with Neu-Laxova syndrome (same case) [ 1 ]


Flupirtine


Niemann–Pick disease has an autosomal recessive pattern of inheritance.


Niemann–Pick Disease in a child, 1968


Typical ossification center formation in a developing long bone of a fetal cat.


Opsismodysplasia has an autosomal recessive pattern of inheritance.


Transmission   electron micrograph  of a  mesenchymal stem cell  displaying typical  ultrastructural  characteristics.


Simplified diagram of MSCs, and their differentiation pathways into osteoblast and chodrocytic cell lineages. Data based on a 10.5-day-old mouse embryo. Included are the multiple factors for differentiation. [ 2 ]


Example of bone deformation


The Latham Device


Post Latham


Nasal Alveolar Molding Device


Post Insertion


Micrograph  of an excised  aortic valve   papillary fibroelastoma  showing that the avascular branching papillae are covered by endothelium.  H&E stain .


TRAP syndrome . The acardiac twin, left, cannot pump its own blood. The pump twin, right, supplies blood to the parasitic twin.


The location of genes on chromosome 12


Radiograph  showing a pelvic digit


Symptoms of Pfeiffer syndrome in a 17-year-old girl, 1895


Symptoms of Pfeiffer syndrome in a Chinese adult, 1927


Craniosynostosis  in phosphate diabetes


Bowed legs in phosphate diabetes


Curvation of spine ( Kyphoscoliosis ) in phosphate diabetes


Fibroblast Growth Factor 23 (FGF23)


A six-month old child with an extra leg


German case, born 1529


A grown steer with five legs.


Piglet with  dipygus  at the  Ukrainian National Chernobyl Museum  in Kyiv


Eight-year-old patient with a severe form of PWS


A Child with  obesity  in PWS [ 50 ]


Proboscis in  Patau syndrome .  Cyclopia  (a single median eye) is associated with  arrhinia  (absence of the nose) and proboscis formation above the eye.


Progressive familial intrahepatic cholestasis is inherited in an  autosomal recessive  pattern.


Portuguese  illustration of a foreign woman with deformities indicative of Proteus syndrome, 1695


Proteus syndrome is an  overgrowth disorder  caused by a rare  genetic mosaicism . A genetic mutation during embryonic development gives rise to overgrowth in a subset of the individual's cells.


Renal lobe (renal cortex  green  with renal pyramid below)


Kidney stone


Hemodialysis


Renal cyst MRI (Contributed by Ptrump16  https://commons.wikimedia.org/wiki/File:Renal_cyst_MRI.jpg )


Telomer-structure


Chr 14


[ 8 ]  A type of anticonvulsant(Carbamazepine)


Café au lait spots


Telomeric ends


Congenital diaphragmatic hernia


Facial features (A), left hand and feet showing broad thumb and big toes (B, C) and X-ray of both hands showing short broad thumbs (D). (Limb Malformations & Skeletal Dysplasia)


Rubinstein–Taybi syndrome is inherited in an  autosomal dominant  fashion.


Elderly woman with craniofacial signs of Saethre-Chotzen syndrome


Hand and foot defects seen in Saethre-Chotzen syndrome


Girl with  epicanthal folds


A diagram showing a complete cleft lip and palate


Symptoms of Saethre-Chotzen syndrome with  microcephaly


Cranial sutures viewed from top of head


SCS occurs when there is a mutation on chromosome 7 in the region 7p21


This condition is inherited in an autosomal dominant manner


Symptoms of Saethre-Chotzen syndrome showing autosomal dominance


Bone segments that are removed in fronto-supraorbital advancement


A child wearing a cranial remolding helmet after surgery.


Role of sepiapterine reductase (SPR, in red) in the biosynthesis of tetrahydrobiopterin. From a review by Wu et al., 2020. [ 13 ]


Sirenomelia


Classification of sirenomelia by the presence or absence of bones within the lower limb.  I) all bones of thigh and lower leg present  II) fused  fibula  III) fibula absent  IV) partially fused femur, fused fibula  V) partially fused femur  VI) fused femur, fused  tibia  VII) fused femur, tibia absent


Sirenomelia in  Les écarts de la nature , 1775


Axial  CT image  showing dextrocardia and situs inversus in a patient with  Kartagener syndrome .


Axial CT image showing situs inversus (liver and IVC on the left, spleen and aorta on the right) in a patient with Kartagener syndrome.


Situs inversus has an  autosomal recessive  pattern of inheritance.


Facial deformities with Smith-Fineman-Myers syndrome


extraction of viscera of a lamb with strophosomia


Signatures and patterns of SVs for deletion (A), novel sequence insertion (B), inversion (C), and tandem duplication (D) in read count (RC), read-pair (RP), split-read (SR), and de novo assembly (AS) methods. [ 29 ]


Tay–Sachs disease is inherited in an  autosomal recessive  pattern.


The  HEXA  gene is located on the long (q) arm of human chromosome 15, between positions 23 and 24.


Founder effects  occur when a small number of individuals from a larger  population  establish a new population. In this illustration, the original population is on the left with three possible founder populations on the right. Two of the three founder populations are genetically distinct from the original population.


Ovarian teratoma with hair inside


Mature teratoma of the mediastinum: A horizontal slice of the resected tumor reveals fibrofatty tissue, calcified areas, and a few cystic spaces lined with smooth membrane and containing a hair. In the left lower corner, the involved B5 bronchus is evident.


CT showing a teratoma of the ovary: fatty formation with a smooth boundary, with a dense part, possibly a tooth.


Micrograph  of a teratoma showing tissue from all three  germ layers :  mesoderm  (immature  cartilage  - left-upper),  endoderm  (gastrointestinal glands - center-bottom) and  ectoderm  (epidermis - right)


Ovarian tumors  by  incidence  and risk of  ovarian cancer , with mature cystic teratoma at bottom and  immature teratoma  at right. [ 55 ]


Infant with tetra-amelia syndrome


Tetra-amelia syndrome has an autosomal recessive pattern of  inheritance .


Nick Vujicic , a   motivational speaker  who was born with tetra-amelia syndrome, speaking during the session "Inspired for a Lifetime" at the Annual Meeting 2011 of the  World Economic Forum  in  Davos , Switzerland, on 30 January 2011. [ 4 ] [ 5 ]


In combination with polydactyly


Delta shaped extra phalanx


Ulnar dimelia, showing clenched position


X-ray of 2-month-old female child with ulnar dimelia


VPI flow chart compiled from the following sources: Johns, Rohrich & Awada, 2003 and Peterson-Falzone, Karnell, Hardin-Jones,& Trost-Cardamone, 2005


The man on the left is illustrated as vestigial parasitic twins, meanwhile on the right there are two varieties of conjoined twins illustrated.


Pictured is a boy that is a vestigial twin. He has a parasitic twins limbs attached to his abdomen.


An infant with a mass of cells connected to their head


An MRI machine may be used to diagnose vestigial twins.


Vici syndrome has an autosomal recessive pattern of inheritance.


SRY Protein


An example of translocation between two chromosomes


8 July: Researchers report that they succeeded in using a  genetically altered variant  of  R. sulfidophilum  to produce  spidroins , the  main  proteins  in  spider silk . [ 70 ]


10 November: Scientists show that  microorganisms could be employed to mine  useful elements from basalt rocks in space. [ 88 ]


25 November: The development of a biotechnology for  microbial reactors  capable of producing oxygen as well as  hydrogen  is reported. [ 92 ]


30 November: The 50-year problem of  protein structure prediction  is reported to be largely solved with an AI algorithm. [ 94 ]


Researchers present a  bioprinting  method to produce steak-like  cultured meat .


The first  CRISPR-edited  food, tomatoes, goes on public sale.


Researchers introduce and demonstrate  the concept of  necrobotics .


Remote controlled   cyborg cockroaches .


A new  CRISPR gene editing/repair tool  alternative to fully active Cas9 is reported.


Wastewater surveillance  is used  to detect monkeypox [ 300 ]


Safety-by-design ways like DNA screening for  biosafety  and  biosecurity  to  prevent engineered pandemics


A bone-like  biocomposite   3D printing  ink, BactoInk


Scientists coin and outline a new field ' organoid intelligence ' (OI)


Cell culture-based coffee [ 360 ] [ 361 ]


Human  karyotype  with annotated bands and sub-bands as used for the  nomenclature of chromosome abnormalities . It shows dark and white regions as seen on  G banding . Each row is vertically aligned at  centromere  level. It shows 22  homologous   autosomal  chromosome pairs, both the female (XX) and male (XY) versions of the two  sex chromosomes , as well as the  mitochondrial genome  (at bottom left).  Further information:  Karyotype


Duchenne muscular dystrophy


Craniosynostosis  can be found in several disorders, like  Carpenter Syndrome


A  ribose  ring with the carbon atoms numbered 1' through 5' according to chemical convention. The  5' carbon  is said to be  upstream ; the  3'   carbon  is said to be  downstream . Bonds to a generic  base  and a  phosphate  group are also shown.


The chemical structure of  acetyl-CoA , with the  acetyl group  highlighted in blue


Every  amino acid  has the same basic structural formula, consisting of a central carbon atom (α) bonded to three major substituents: one  amino group  (blue), one  carboxyl group  (red), and one variable  side chain  (green). The side chain, which can range from a simple  methyl  group ( alanine ) to more complex functional groups such as a double-ringed  indole  ( tryptophan ), gives each particular amino acid its unique identity. During  translation , amino acids are joined into a linear chain by condensation reactions which create  peptide bonds  between the carboxyl group of one amino acid and the amino group of an adjacent amino acid. The first and last amino acids in the chain are said to be  N-terminal  and  C-terminal , respectively, in reference to the unbonded amino group of the first amino acid and the unbonded carboxyl group of the last.


The  apical constriction  of specific groups of cells during developmental morphogenesis allows bends and turns to form in higher-order tissues.


The three principal biologically active conformations of  DNA  molecules:  A-DNA ,  B-DNA , and  Z-DNA  (left to right), as viewed from the side and down the axis of the  double helix .


Cross-sectional diagram of a typical eukaryotic  cell membrane


Possible types of information transfer according to the  central dogma of molecular biology . Three general transfers, in red, occur routinely in all living cells: DNA-to-DNA ( DNA replication ), DNA-to-RNA ( transcription ), and RNA-to-protein ( translation ). Three special transfers, in blue, are known to occur only in viruses or in the laboratory: RNA-to-RNA ( RNA replication ), RNA-to-DNA ( reverse transcription ), and DNA-to-protein (direct translation without an mRNA intermediate). An additional three transfers are believed not to be possible at all: protein-to-protein, protein-to-RNA, and protein-to-DNA—though it has been argued that there are exceptions by which all three can occur.


Deoxyribose  differs from  ribose  only at the 2' carbon, where ribose has an oxygen atom that deoxyribose lacks (hence its name).


A diagram of the many components of  DNA replication


The molecular structures of several common classes of  DNA-binding domains  (grey), showing how they interact with the DNA double helix (blue)


Double-stranded DNA most commonly exists in the shape of a  double helix .


Different forms of  endocytosis


Plasmid map of a 3,756- bp   expression vector  used in the expression of a  transgene  that makes  green fluorescent protein  (GFP). The vector also includes a gene for the  lac  repressor  (lacI) and a gene conferring resistance to the antibiotic  kanamycin  (KanR), as well as various  promoters  for driving the expression of these genes.


The  karyotype  of a typical human male, as visualized in a karyogram using  Giemsa staining


The structure of a typical mature protein-coding  messenger RNA  or  mRNA , drawn approximately to scale. The coding sequence (green) is bounded by  untranslated regions  at both the  5'-end  (yellow) and the  3'-end  (pink). Prior to export from the nucleus, a  5' cap  (red) and a  3' poly(A) tail  (black) are added to help stabilize the mRNA and prevent its degradation by ribonucleases.


An outline of how  molecular cloning  works


The  nucleobases  (blue) are the five specific  nitrogenous bases  canonically used in DNA and RNA. A nucleobase bonded to a  pentose  sugar (either  ribose  or  deoxyribose ; yellow) is known as a  nucleoside  (yellow + blue). A nucleoside bonded to a single  phosphate group  (red) is known as a nucleoside monophosphate (NMP) or a  nucleotide  (red + yellow + blue). When not incorporated into a nucleic acid chain, free nucleosides can bind multiple phosphate groups: two phosphates yields a  nucleoside diphosphate  (NDP), and three yields a  nucleoside triphosphate  (NTP).


A defining element of nucleic acid structure is the linear chain of alternating  sugars  (orange) and  phosphates  (yellow) known as the  phosphate backbone , which acts as a scaffold to which  nucleobases  are attached. The phosphorus atom of each phosphate group forms two  ester bonds  to specific carbon atoms within the pentose sugars— ribose  in RNA and  deoxyribose  in DNA—of two adjacent nucleosides.


A cell's  ploidy  level is defined by the number of copies it has of each specific chromosome: if the cell has two copies of each of three distinct chromosomes, it is said to be  diploid  (2N).


A  reciprocal translocation  between chromosome 4 and chromosome 20


A double-stranded DNA molecule containing the sequence  GAATTC  and its palindromic complement  CTTAAG , a  restriction site  for the bacterial enzyme  EcoRI , is recognized and  cut or "digested"  in the manner shown here, with the enzyme breaking phosphodiester bonds in the backbones of both strands and leaving behind  "sticky" overhangs  at the ends of each of the now separate molecules.


An outline of the  Sanger sequencing  method


Three different modes of  DNA replication . In  semiconservative replication , each of the two daughter molecules is built from one of the original parental strands and one newly synthesized strand. In  conservative replication , the original parent molecule remains intact while the replicated molecule is composed of two newly synthesized strands. In  dispersive replication , each of the daughter molecules is an uneven mix of old and new, with some segments consisting of the two parental strands and others consisting of two newly synthesized strands. Only semiconservative replication occurs naturally.


A  sequence logo  depicts the statistical frequency with which each nucleobase (or amino acid) occurs within a given  sequence . Each position in the sequence is represented by a vertical stack of letters; the total height of the stack indicates the degree of  consensus  at that position between all of the aligned sequences, and the height of each individual letter in the stack indicates the proportion of the aligned sequences having that nucleobase at that position. A single very large letter filling most of the stack indicates that most or all of the aligned sequences have that particular nucleobase at that position.


The  standard genetic code  specifies a set of 20 different  amino acids  from triplet arrangements of the four different  RNA   nucleobases  ( A ,  G ,  C , and  U ). To read this chart, choose one of the four letters in the innermost ring and then move outward, adding two more letters to complete a  codon  triplet: a total of 64 unique codons can be made this way, 61 of which signal the addition of one of the 20 amino acids (identified by single-letter abbreviation as well as by full name and chemical structure) to a nascent  peptide  chain, while the remaining three codons are  stop codons  signalling the termination of translation. Also indicated are some of the chemical properties of the amino acids and the various ways in which they can be modified.


A simplified diagram of  transcription . RNA polymerase (RNAP) synthesizes an RNA transcript (blue) in the 5'-to-3' direction, using one of the DNA strands as a  template , while a complex of multiple  transcription factors  binds to a  promoter  upstream of the gene.


Contemporary human mtDNA haplogroup distribution, based on analysis of 2,054 individuals from 26 populations. [ 1 ]  (a) Pie charts on the map. (b) Counts of haplogroups in table format. For populations details, see  1000 Genomes Project#Human genome samples .


mtDNA haplogroup tree and distribution map. [ 3 ]  The numbers are haplogroup labels, reported according to the  http://www.phylotree.org/  nomenclature, [ 4 ]  and give the location of one of the mutations leading to the derived haplotype. (Only a single branch defining marker, preferably from the coding region, is shown.) The main geographic features of haplogroup distribution are highlighted with colour.


Dispersal route of human mtDNA haplogroups


Estimated world map of human migrations based on mtDNA haplogroups.


Human Y-DNA phylogeny and haplogroup distribution. [ 1 ] (a)  Phylogenetic tree . 'kya' means 'thousand years ago'.  (b) Geographical distributions of haplogroups are shown in color.  (c) Geographical color legend.


Schematic illustration of Y-DNA haplogroups naming convention. Haplogroups are defined through mutations (SNPs).


Migration route of Human Y-chromosome DNA haplogroups.


The hypothetical divergence of Haplogroup R and its descendants.


Farmers with wheat and cattle—Ancient Egyptian art 1,422 BCE displaying domesticated animals


Galton in his later years


Pedigree chart  showing an  inheritance pattern  consistent with  autosomal dominant  transmission. Behavioural geneticists have used  pedigree studies  to investigate the genetic and environmental basis of behaviour.


Study results about which and to what degree various traits, IQ and language-related  skills  appear to be  influenced by genetics [ 45 ] [ 46 ]


Similarity in twins and adoptees indicates a small role for shared environment in  personality .


Modifications of the  epigenome  do not alter DNA.


Monozygotic twins  are identical twins.  Twin studies  help to reveal epigenetic differences related to various aspects of psychology.


The  hypothalamic pituitary adrenal axis  is involved in the  human stress response .


In the 2011 study by neuroscientist Ryota Kanai (n=90 students), the subjects who expressed  conservative  views (right) tended to have a larger amygdala than those who expressed  liberal  views (left).


Identical twin studies are a useful mechanism for assessing the role of genes and environment


Suicide rate in Hungary (1950–2005), 1983: 45.3 suicides per 100,000 people, it was the second highest rate (after Lithuania, 1995: 45.6 [ 1 ] ) of an independent state in recorded human history. Higher rates were only measured in regions like Greenland or the Canadian territories.


Lewis Terman, founder of the Genetic Studies of Genius


A 1680 painting by  Juan Carreño de Miranda  of a girl presumed to have  Prader-Willi syndrome [ 1 ]


Francis Galton


Human karyogram


Seymour Benzer in his office at Caltech in 1974 with a big model of Drosophila


Drosophila


Zebrafish


Traits, IQ& language skills


Outward displays of aggression are seen in most animals


Shh and BMP gradient in the neural tube


Brain slices of wildtype and reeler mice


Corticogenesis in a wild-type mouse. First neurons to take their place are the  subplate  neurons (yellow). Next come the cortical plate neurons (black), which migrate past the subplate level. Later-generated neurons drawn to be increasingly more bright.


Corticogenesis in a reeler mutant mouse. Note the so-called "inverted cortex", disorganized cellular layers, oblique angles of radial  glia  fibers.


Tyron's rat chart


Gustav III  of  Sweden  was the first to use identical twins in a comparative study of medical outcomes.


Francis Galton  laid the foundations of  behavior genetics  as a branch of  science .


A : ACE model showing raw (non-standardised) variance coefficients


B : ACE model showing standardised variance coefficients


A depiction of MZ-discordance data


MZ discordant test of hypothesis that exercise protects against depression