Sequence variation within the fragile x locus

The human genome provides a reference sequence, which is a template for res equencing studies that aim to discover and interpret the record of common a ncestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we presen t a study of similar to 31 kb spanning an similar to 70 kb region of FMR1, sequenced in a sample of 20 humans (worldwide sample) and four great apes ( chimp, bonobo, and gorilla). Twenty-five polymorphic sites and two insertio n/deletions, distributed in It unique haplotypes, were identified among hum ans. Africans are the only geographic group that do not share any haplotype s with other groups. Parsimony analysis, reveals two main clades and sugges ts that the four major human geographic groups are distributed throughout t he phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three ot her geographic groups. Nucleotide diversity, pi, for this sample is 2.63 +/ - 6.28 x 10(-4). The mutation rate, mu, is 6.48 x 10(-10) per base pair per year, giving an ancestral population size of similar to 6200 and a time to the most recent common ancestor of similar to 320,000 +/- 72,000 per base pair per year. Linkage disequilibrium (LD) at the FMR1 locus, evaluated by conventional LD analysis and by the length of segment shared between any tw o chromosomes, is extensive across the region.