1. ¹Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA
2. ²Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
3. ³Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA
4. ⁴Department of Obstetrics and Gynecology, Faculty of Medicine, University of Benin, Benin City, Nigeria
5. ⁵Department of Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence: Dr KK Kidd, Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8005, USA. Tel.: +1 203 785 2654; fax: +1 203 785 6568; E-mail: Kidd@biomed.med.yale.edu

Received 2 December 2002; Revised 9 April 2003; Accepted 11 April 2003.

Abstract

We have constructed haplotypes based on normal variation at six polymorphic sites–five single nucleotide polymorphisms (SNPs) and one short tandem repeat polymorphism (STRP)–at the RET locus for samples of normal individuals from 32 populations distributed across the major continental regions of the world. The haplotyped system spans 41.6 kilobases and encompasses most of the coding region of the gene. All of the markers are polymorphic in all regions of the world and in most individual populations. Expected heterozygosities for the six-site haplotypes range from 82 to 94% for all populations studied except for two Amerindian groups from the Amazon basin at 61 and 76%. Individual populations had from four to eight haplotypes with frequencies exceeding 5%. In general, African, southwest Asian and European groups have the highest numbers of total and of commonly occurring haplotypes; the lowest numbers are observed in Amerindian populations. Overall linkage disequilibrium (LD) for the five SNP sites was very significant (P0.001) for all the non-African populations, but significant at that level for only one of the seven African populations. In general, the permutation-based coefficient that quantifies overall LD tends to increase the farther the population is from Africa, but variability of this measure of LD is often large within geographic regions. Pairwise LD measures among the SNPs also show considerable variation among populations. Association of STRP alleles with the SNP-defined background haplotypes is generally higher outside of Africa than in Africa, but is highly variable.