Genomics Chapter 18

Mapping Genomes Genetic maps Physical maps Abstract maps that place the relative location of genes on chromosomes based on recombination frequency Physical maps Use landmarks within DNA sequences, ranging from restriction sites to the actual DNA sequence

First genetic maps were linkage maps Distances reflected recombination frequencies between genes Measured in centimorgans (cM) Limitations Distances between genes determined by recombination frequencies do not directly correspond to physical distance on a chromosome Conformation of DNA can affect frequency of recombination Not all genes have obvious phenotypes to look for in crosses

Whole Genome Sequencing The ultimate physical map is the base-pair sequence of the entire genome Automation of this process increased the rate of sequence generation Genome sequencing is one case in which technology drove the science, rather than the other way around

To reduce errors, 5–10 copies of a genome are sequenced and compared Sequencers provide accurate sequences for DNA segments up to 800 bp long To reduce errors, 5–10 copies of a genome are sequenced and compared Vectors used to clone large pieces of DNA Yeast artificial chromosomes (YACs) Bacterial artificial chromosomes (BACs) Human artificial chromosomes (HACs)

The Human Genome Project Originated in 1990 by the International Human Genome Sequencing Consortium Goal of this publicly funded effort was to use a clone-by-clone approach to sequence the human genome Craig Venter formed a private company and entered the “race” in May, 1998 Using shotgun-sequencing In 2001, both groups published a draft sequence Gaps in sequence still being filled Still being revised

The Human Genome Project In 2004, the “finished” sequence was published as the reference sequence (REF-SEQ) in databases -3.2 gigabasepairs -1 Gb = 1 billion basepairs -Contains a 400-fold reduction in gaps -99% of euchromatic sequence -Error rate = 1 per 100,000 bases

Characterizing Genomes The Human Genome Project found fewer genes than expected -Initial estimate was 100,000 genes -Number now appears to be about 25,000! In general, eukaryotic genomes are larger and have more genes than those of prokaryotes -However, the complexity of an organism is not necessarily related to its gene number

Genome Organization Genomes consist of two main regions -Coding DNA -Contains genes than encode proteins -Noncoding DNA -Regions that do not encode proteins

Coding DNA in Eukaryotes Four different classes are found: -Single-copy genes: Includes most genes -Segmental duplications: Blocks of genes copied from one chromosome to another -Multigene families: Groups of related but distinctly different genes -Tandem clusters: Identical copies of genes occurring together in clusters -Also include rRNA genes

Noncoding DNA in Eukaryotes Each cell in our bodies has about 6 feet of DNA stuffed into it -However, less than one inch is devoted to genes! Six major types of noncoding human DNA have been described

Noncoding DNA in Eukaryotes Noncoding DNA within genes -Protein-encoding exons are embedded within much larger noncoding introns Structural DNA -Called constitutive heterochromatin -Localized to centromeres and telomeres Simple sequence repeats (SSRs) -One- to six-nucleotide sequences repeated thousands of times

Noncoding DNA in Eukaryotes Segmental duplications -Consist of 10,000 to 300,000 bp that have duplicated and moved Pseudogenes -Inactive genes

Noncoding DNA in Eukaryotes Transposable elements (transposons) -Mobile genetic elements -Four types: -Long interspersed elements (LINEs) -Short interspersed elements (SINEs) -Long terminal repeats (LTRs) -Dead transposons

Variation in the Human Genome Single-nucleotide polymorphisms (SNPs) are sites where individuals differ by only one nucleotide -Must be found in at least 1% of population Haplotypes are regions of the chromosome that are not exchanged by recombination -Tendency for genes not to be randomized is called linkage disequilibrium -Can be used to map genes

Genomics Organellar genomes -Mitochondria and chloroplasts are descendants of ancient endosymbiotic bacterial cells -Over time, their genomes exchanged genes with the nuclear genome -Both organelles contain polypeptides encoded by the nucleus

Genomics Transgenics is the creation of organisms containing genes from other species (transgenic organisms) -Can be used to determine whether: -A gene identified by an annotation program is really functional in vivo -Homologous genes from different species have the same function

Applications of Genomics Genomics has also helped in agriculture -Improvement in the yield and nutritional quality of rice -Doubling of world grain production in last 50 years, with only a 1% cropland increase

Applications of Genomics Genome science is also a source of ethical challenges and dilemmas -Gene patents -Should the sequence/use of genes be freely available or can it be patented? -Privacy concerns -Could one be discriminated against because their SNP profile indicates susceptibility to a disease?