Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the jirel ethnic group in eastern nepal

Kimberly D. Williams, John Blangero, Janardan Subedi, Bharat Jha, Thomas Dyer, John L. Vandeberg, Bradford Towne, Sarah Williams-Blangero

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Objectives: There is phenotypic overlap between Brachydactyly Type D (BDD) and Brachydactyly Type E (BDE) that suggests a possible common underlying etiology. We seek to understand the genetic underpinnings of, and relationship between, these skeletal anomalies. Methods: The Jirel ethnic group of eastern Nepal participates in various genetic epidemiologic studies, including those in which hand-wrist radiographs have been taken to examine skeletal development. Nearly 2,130 individuals (969 males; 1,161 females) were phenotyped for BDD/BDE. Of these, 1,722 individuals (773 males; 949 females) were genotyped for 371 STR markers spanning the autosomal genome. Variance components-based linkage analysis was used to conduct a genome-wide linkage scan for QTL influencing the BDD/BDE phenotype. Results: BDD was present in 3.55%, and BDE was present in 0.39%, of the study sample. Because of the phenotypic overlap between two traits, affecteds of either type were considered as affected by a single combined phenotype (BDD/BDE) having a prevalence of 3.94%. The additive genetic heritability of BDD/BDE was highly significant (h2 ± SE = 0.89 ± 0.13; P = 1.7 × 10-11). Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516). Conclusions: Possible positional candidate genes in the one-lod support interval of this QTL include TWIST and the HOXA1-A13 cluster. This is the first study to report significant linkage results for BDD/BDE using a large extended pedigree, and the first to suggest that mutations in TWIST and/or the HOXA1-A13 cluster may contribute to these specific skeletal anomalies. Am. J. Hum. Biol. 25:743-750, 2013.

Original languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalAmerican Journal of Human Biology
Issue number6
StatePublished - Nov 2013
Externally publishedYes

ASJC Scopus subject areas

  • Anatomy
  • Ecology, Evolution, Behavior and Systematics
  • Anthropology
  • Genetics


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