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

Journal Article · Tue Nov 01 04:00:00 EST 1994 · American Journal of Human Genetics

OSTI ID:56841

Sulisalo, T; Klockars, J; Chapelle, A de la ^[1]; Kaitila, I ^[1]; Maekitie, O ^[2]; Sistonen, P ^[3]; Francomano, C A ^[4]

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1. Univ. of Helsinki (Finland)
2. Helsinki Univ. Central Hospital (Finland)
3. Finnish Red Cross Blood Transfusion Service, Helsinki (Finland)
4. Johns Hopkins Hospital, Baltimore, MD (United States)

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 Delbrueck (1943) method and adapted to the study of human founder populations suggests that the distance between CHH and D9S163 is {approximately}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. 21 refs., 4 figs., 3 tabs.

• OSTI ID: 56841
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CARTILAGE
CHROMOSOMAL ABERRATIONS
FINLAND
GENE MUTATIONS
GENES
GENETIC MAPPING
HAIR
HEREDITARY DISEASES
HUMAN CHROMOSOME 9
HUMAN POPULATIONS
SKELETAL DISEASES
STATISTICAL MODELS