A Locus for Brachydactyly Type A-1 Maps to Chromosome 2q35-q36

Abstract

Brachydactyly type A-1 (BDA1) was, in 1903, the first recorded example of a human anomaly with Mendelian autosomal dominant inheritance. Two large families, the affected members of which were radiographed, were recruited in the study we describe here. Two-point linkage analysis for pedigree 1 (maximum LOD score [Zmax] 6.59 at recombination fraction [theta] 0.00) and for pedigree 2 (Zmax=5.53 at straight theta=0.00) mapped the locus for BDA1 in the two families to chromosome 2q. Haplotype analysis of pedigree 1 confined the locus for family 1 within an interval of <8.1 cM flanked by markers D2S2248 and D2S360, which was mapped to chromosome 2q35-q36 on the cytogenetic map. Haplotype analysis of pedigree 2 confined the locus for family 2 within an interval of <28. 8 cM flanked by markers GATA30E06 and D2S427, which was localized to chromosome 2q35-q37. The two families had no identical haplotype within the defined region, which suggests that the two families were not related.

Answering a century old riddle: brachydactyly type A1

“…One year later, Gao et al [17] (2001), working in the same lab as Yang, recruited a new BDA1 family in the study. In x-ray analysis, it showed that the hand bones of affected members had the same morphology ( Fig 2B) as those seen in families studied by Yang et al (2000)[16] but short stature in affected members was a significant feature.…”

“…Yang et al [16] in 2000 described two large Chinese BDA1 families, of which family I showed all the manifestations that are common to other reports reviewed by Fitch 1979[22]. However, several affected members had some manifestations beyond Fitch's description including the shortened distal phalanges, metacarpals and proximal phalange of digit 5.…”

“…Mastrobattista [12](1995) excluded a number of candidate genes in his study of two families with multiple affected members. Yang et al [16] (2000) and Gao et al [17] (2001) went further by mapping and identifying the gene for Brachydactyly type A1, IHH (Indian hedgehog), using their own samples. Their works have shed light on the BDA1-causing gene with leading to a number of papers published.…”

A novel locus for parietal foramina maps to chromosome 4q21-q23

“…Genotyping and linkage analysis Samples of peripheral blood were taken from all available family members, and DNA was isolated by means of the laboratory procedure described elsewhere (Yang et al 2000). First, a search was carried out on both chromosomes 11 and 5, because ALX4 was located on the former and MSX2 on the latter chromosome.…”

A novel heterozygous mutation in the Indian hedgehog gene (IHH) is associated with brachydactyly type A1 in a Chinese family

“…The gene for BDA1 was mapped to 2q35-q36 by linkage analysis in two Chinese families (Yang et al 2000). Subsequently, three distinct mutations were identified within the Indian hedgehog gene (IHH) (Gao et al 2001).…”