Journal article
A single-gene explanation for the probability of having idiopathic talipes equinovarus
American journal of human genetics, Vol.53(5), pp.1051-1063
11/1993
PMCID: PMC1682321
PMID: 8213831
Abstract
It has been hypothesized that the pathogenesis of idiopathic talipes equinovarus (ITEV, or clubfoot) is explained by genetic regulation of development and growth. The objective of the present study was to determine whether a single Mendelian gene explains the probability of having ITEV in a sample of 143 Caucasian pedigrees from Iowa. These pedigrees were ascertained through probands with ITEV. Complex segregation analyses were undertaken using a regressive logistic model. The results of these analyses strongly rejected the hypotheses that the probability of having ITEV in these pedigrees was explained by a non-Mendelian pattern of transmission with residual sibling correlation, a nontransmitted (environmental) factor with residual sibling correlation, or residual sibling correlation alone. These results were consistent with the hypothesis that the probability of having ITEV was explained by the Mendelian segregation of a single gene with two alleles plus the effects of some unmeasured factor(s) shared among siblings. The segregation of alleles at this single Mendelian gene indicated that the disease allele A was incompletely dominant to the nondisease allele B. The disease allele A, associated with ITEV affection, was estimated to occur in the population of inference with a frequency of .007. After adjusting for sex-specific population incidences of ITEV, the conditional probability (penetrance) of ITEV affection given the AA, AB, and BB genotypes was computed to be 1.0, .039, and .0006, respectively. Individual pedigrees in this sample that most strongly supported the single Mendelian gene hypothesis were identified. These pedigrees are candidates for genetic linkage analyses or DNA association studies.
Details
- Title: Subtitle
- A single-gene explanation for the probability of having idiopathic talipes equinovarus
- Creators
- T R Rebbeck - Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111F R Dietz - Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111J C Murray - Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111K H Buetow - Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.53(5), pp.1051-1063
- PMID
- 8213831
- PMCID
- PMC1682321
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 11/1993
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025425702771
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