PKLR- GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations

Hum Genet. 2002 Jun;110(6):532-44. doi: 10.1007/s00439-002-0734-2. Epub 2002 May 22.


Haplotype diversity in a genomic region of approximately 70 kb in 1q21 between genes PKLR and GBA was characterized by typing one single nucleotide polymorphism (SNP) in PKLR, two SNPs in GBA and one short tandem repeat polymorphism (STRP) in PKLR in 1792 chromosomes from 17 worldwide populations. Two other SNPs in GBA were typed in three African populations. Most chromosomes carried one of either two phylogenetically distinct haplotypes with different alleles at each site. Allele diversity at the STRP was tightly linked to haplotype background. Linkage disequilibrium (LD) was highly significant for all SNP pairs in all populations, although it was, on average, slightly higher in non-African populations than in sub-Saharan Africans. Variation at PKLR-GBA was also tightly linked to that at the GBA pseudogene, 16 kb downstream from GBA. Thus, a 90 kb-long LD block was observed, which points to a low recombination rate in this region. Detailed haplotype phylogeny suggests that the chimpanzee GBA haplotype is not one of the two most frequent haplotypes. Based on variability at the PKLR STRP and on the geographical distribution of LD, the expansion of the two main haplotypes may have predated the "Out of Africa" expansion of anatomically modern humans. LD and STRP variability in non-Africans are approximately 87% of those in Africans, in contrast with other loci; this implies that the "out of Africa" bottleneck may have had a broad distribution of effects across loci.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa
  • Alleles
  • Animals
  • Base Sequence
  • Chromosomes, Human, Pair 1 / genetics*
  • Evolution, Molecular
  • Gene Frequency
  • Genetic Variation
  • Genetics, Population
  • Glucosylceramidase / genetics*
  • Haplotypes
  • Hominidae / genetics
  • Humans
  • Linkage Disequilibrium*
  • Models, Genetic
  • Pan troglodytes / genetics
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Pseudogenes
  • Pyruvate Kinase / genetics*
  • Selection, Genetic
  • Tandem Repeat Sequences


  • Pyruvate Kinase
  • Glucosylceramidase