High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene

Tuija Sulisalo, Jaakko Klockars, Outi Mäkitie, Clair A. Francomano, Albert De La Chapelle, Ilkka Kaitila, Pertti Sistonen

Research output: Contribution to journalArticle

Abstract

We recently assigned the gene for an autosomal recessive skeletal dysplasia, cartilage-hair hypoplasia (CHH), to 9p21-p13 in Finnish and Amish families. An association was observed between CHH and alleles at D9S163 in both family series, suggesting that these loci are in linkage disequilibrium and close to each other. Here we extended these studies by exploiting the linkage-disequilibrium information that can be obtained from families with a single affected child, and we studied 66 Finnish CHH families with seven microsatellite markers. The analysis based on the Luria and Delbruck (1943) method and adapted to the study of human founder populations suggests that the distance between CHH and D9S163 is ~0.3 cM. An eight-point linkage analysis modified to take advantage of all possible information in 15 Finnish and 17 Amish families was capable of narrowing the likely location of CHH to within an interval of 1.7 cM on a male map. The peak lod score of 54.92 was attained 0.03 and 0.1 cM proximal to D9S163 on the male and female maps, respectively. These results confirm the power of genetic resolution, that lies in the study of linkage disequilibrium in well-defined founder populations with one major ancestral disease mutation.

Original languageEnglish (US)
Pages (from-to)937-945
Number of pages9
JournalAmerican journal of human genetics
Volume55
Issue number5
StatePublished - Nov 1 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Sulisalo, T., Klockars, J., Mäkitie, O., Francomano, C. A., De La Chapelle, A., Kaitila, I., & Sistonen, P. (1994). High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene. American journal of human genetics, 55(5), 937-945.