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

Abstract

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. 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.

The Prevalence of Glaucoma in the Jirel Ethnic Group of Nepal

“…The Jirel population has been the focus of a broad range of anthropological and biomedical studies for more than three decades. These studies have included anthropological investigations ( 23 ), assessments of population structure ( 24 ), studies of genetic susceptibility to parasitic worm infection ( 25 ), and studies of the genetics of growth and development ( 26 ). Current research in the Jirel population is focused on the genetic epidemiology of ocular traits and disorders as part of the Jiri Eye Study (JES) ( 27 ).…”

Glycated Serum Protein Genetics and Pleiotropy with Cardiometabolic Risk Factors

“…The Jirel Family Studies began in 1987 and focused on the Jirel population of eastern Nepal. Approximately 2,500 members of the Jirel population have participated in prior studies including anthropological investigations [16, 17], assessments of population structure [18, 19], genetic epidemiology studies of susceptibility to parasitic worm infections [20, 21], genetic studies of growth and development [22, 23], and investigations of the genetics of ocular disease [24]. The long running research conducted in the region has resulted in the collection of extensive genealogical information on the Jirel people.…”

Quantitative physical activity assessment of children and adolescents in a rural population from Eastern Nepal

“…The Jirels have been the focus of extensive genetic and epidemiological studies for over 25 years (e.g., Blangero, ; Relethford and Blangero, ; Williams‐Blangero, ,,, , , , ; Williams‐Blangero and Blangero, , Williams‐Blangero et al, ). All subjects in this study were participants in the Jiri Growth Study (Williams et al, , , , ), a genetic epidemiological study of growth and development. The Jiri Growth Study began in 2000, and from 2005 to 2012, objective physical activity assessment was collected.…”