法测定急性淋巴细胞白血病患儿血清中课件.ppt

Population Genomics Gil McVean, Department of Statistics, Oxford Questions about genetic variation How different are our genomes? How is the variation distributed within and between genomes? What does variation tell us about human evolution? How different are our genomes? Serological techniques for detecting variation Blood group systems in humans 28 known systems 39 genes, 643 alleles Protein electroporesis Changes in mass/charge ratio resulting from amino acid substitutions in proteins can be detected In humans, about 30% of all loci show polymorphism with a 6% chance of a pair of randomly drawn alleles at a locus being different The rise of DNA sequence analysis RFLPs Cann et al 1987 Sequencing of small regions Vigilant et al 1991 Whole genome sequencing Ingman et al 2000 The human genomes… The draft human genome sequence was published in 2001 This is a mosaic from several individuals Since then, several more genomes have been sequenced, at least partially Shotgun sequencing variation discovery Other methods have been developed to look for gross chromosomal differences The International HapMap Project Launched in 2002 with the goal of characterising single nucleotide variation between 540 human genomes from individuals of European, Nigerian, Chinese and Japanese ancestry Not a sequencing project, rather it types known polymorphisms Has currently assembled information on over 6 million SNPs (single nucleotide polymorphisms) The 1000 Genomes Project How do we differ? – Let me count the ways Single nucleotide polymorphisms 1 every few hundred bp Short indels (=insertion/deletion) 1 every few kb Microsatellite (STR) repeat number 1 every few kb Minisatellites 1 every few kb Repeated genes rRNA, histones Large inversions, deletions Y chromosome, Copy Number Variants (CNVs) Y chromosome variation Non-pathological rearrangements of the AZFc region on the Y chromosome Mutation is the ultimate source of variation New mutations occur in the g