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GENERAL VIEW OF THE HUMAN GENOME. Gene landscape. In prokaryotes, genes are often tandemly arranged, with little or no spacer sequences in between In eukaryotes, there is considerable spacer DNA between genes
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Gene landscape • In prokaryotes, genes are often tandemly arranged, with little or no spacer sequences in between • In eukaryotes, there is considerable spacer DNA between genes • some is repetitive DNA: identical or nearly identical repeated units (much is derived from mobile genetic elements) • …but also are unique sequences
Segmental duplications (low-copy repeats) • Large block (1 >200Kb) • Highly Similar (>97%) • Without characteristic sequences A’ A
3) Segmental duplications • Closely related sequence blocks at different genomic loci • Transfer of 1-200kb blocks of genomic sequence • Segmental duplications can occur on homologous chromosomes (intrachromosomal) or non homologous chromosomes (interchromosomal) • Not always tandemly arranged • Relatively recent (population polymorphisms) • Found especially around centromeres and telomeres
Segmental duplications Intrachromosomal duplications occur within a chromosome / arm Interchromosomal segments duplicated among non-homologous chromosomes Nature Reviews Genetics2, 791-800 (2001);
Duplications (and rearrangements) are very common: intrachromosomal
SEGMENTAL DUPLICATIONS ON CHROMOSOME 9: IINTERCHROMOSOMAL DUPLICATIONS LARGE DUPLICATIONS (GREATER THAN 10 kb) ARE SHOWN WITH CHROMOSOME 9 MAGNIFIED; OTHER CHROMOSOMES ARE ARRANGED IN THE ORDER IN WHICH THEY MATCH CHROMOSOME (GRAY RECTANGLE IS HETEROCHROMATIN) HUMPHRAY et al. (2004), Nature429, 369-374
CNVs IN POPULATIONS Recent segmental duplications are polymorphic CNVs AND DISEASE
(SSRs) (about 3% of Human Genome)
Variable Nucleotide Tandem Repeats (VNTRs) • VNTRs are short segments of DNA that repeat a few to hundreds of times • These unusual repeats occurs many different spots on human chromosomes • Each individual will have different numbers of these VNTRs at each of these spots • Each of these spots, or loci, are given different names (MSRs, STRs, AmpFLPs, etc) • VNTRs are inheritable – the numbers of repeats at each location in you are a random combination of the VNTRs in your parents
Practical Applications with VNTR’s1.Genetic Identification Services (GIS) was established in 1994 to serve the agriculture, aquaculture, and wildlife ecology communities through the development and use of custom genetic markers for a wide variety of applications. GIS has developed libraries for academic, commercial, and government entities. GIS has also developed a data base of loci in studies involving a wide range of plant and animal species. EXAMPLES OF GIS APPLICATIONSIdentification of economically important genetic traits Selective breeding Population structure and dynamics Monitoring genetic diversity Wildlife forensics Proprietary stock and strain protection Parent-offspring identification Sexing
PROBLEMS with determining a reasonable VNTR “match”VNTRs, are not distributed evenly across all of human population. A given VNTR cannot, therefore, have a stable probability of occurrence; it will vary depending on an individual's genetic background. The difference in probabilities is particularly visible across racial lines. Some VNTRs that occur very frequently among Hispanics will occur very rarely among Caucasians or African-Americans. Additionally, the heterogeneous genetic composition of interracial individuals, who are growing in number, presents an entirely new set of questions. This type of population genetics has been hindered by controversy, because the idea of identifying people through genetic anomalies along racial lines comes alarmingly close to the eugenics and ethnic purification movements and, some argue, could provide a scientific basis for racial discrimination.
transposase gene IR IR DNA TE transposition DNA break repair of double-strand break, using sister chromatid
