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. 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 language | English (US) |
|---|---|
| Pages (from-to) | 743-750 |
| Number of pages | 8 |
| Journal | American Journal of Human Biology |
| Volume | 25 |
| Issue number | 6 |
| DOIs | |
| State | Published - Nov 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Anthropology
- Anatomy
- Genetics
- Ecology, Evolution, Behavior and Systematics
Cite this
Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the jirel ethnic group in eastern nepal. / Williams, Kimberly D.; Blangero, John; Subedi, Janardan; Jha, Bharat; Dyer, Thomas; Vandeberg, John L.; Towne, Bradford; Williams-Blangero, Sarah.
In: American Journal of Human Biology, Vol. 25, No. 6, 11.2013, p. 743-750.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the jirel ethnic group in eastern nepal
AU - Williams, Kimberly D.
AU - Blangero, John
AU - Subedi, Janardan
AU - Jha, Bharat
AU - Dyer, Thomas
AU - Vandeberg, John L.
AU - Towne, Bradford
AU - Williams-Blangero, Sarah
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84886293033&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886293033&partnerID=8YFLogxK
U2 - 10.1002/ajhb.22441
DO - 10.1002/ajhb.22441
M3 - Article
C2 - 24022874
AN - SCOPUS:84886293033
VL - 25
SP - 743
EP - 750
JO - American Journal of Human Biology
JF - American Journal of Human Biology
SN - 1042-0533
IS - 6
ER -