Sequence variation within the fragile X locus

Genome Res. 2001 Aug;11(8):1382-91. doi: 10.1101/gr.172601.

Abstract

The human genome provides a reference sequence, which is a template for resequencing studies that aim to discover and interpret the record of common ancestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we present a study of approximately 31 kb spanning an approximately 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 insertion/deletions, distributed in 11 unique haplotypes, were identified among humans. Africans are the only geographic group that do not share any haplotypes with other groups. Parsimony analysis reveals two main clades and suggests that the four major human geographic groups are distributed throughout the phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three other 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 approximately 6200 and a time to the most recent common ancestor of approximately 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 two chromosomes, is extensive across the region.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics
  • Genetic Markers / genetics
  • Genetic Variation / genetics*
  • Gorilla gorilla
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Microsatellite Repeats / genetics
  • Nerve Tissue Proteins / genetics*
  • Pan paniscus
  • Pan troglodytes
  • Phylogeny
  • Polymorphism, Genetic / genetics
  • RNA-Binding Proteins / genetics
  • Recombination, Genetic / genetics

Substances

  • FMR1 protein, human
  • Genetic Markers
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein