American journal of human biology : the official journal of the Human Biology Council · 2013
Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Williams Kimberly D, Blangero John, Subedi Janardan, Jha Bharat, Dyer Thomas, Vandeberg John L, Towne Bradford, Williams-Blangero Sarah
Аннотация
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 (h(2) ± 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.
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 (h(2) ± 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.