A single-gene explanation for the probability of having idiopathic talipes equinovarus

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 o...

Full description

Saved in:
Bibliographic Details
Published in:American journal of human genetics 1993-11, Vol.53 (5), p.1051-1063
Main Authors: REBBECK, T. R, DIETZ, F. R, MURRAY, J. C, BUETOW, K. H
Format: Article
Language:English
Subjects:
alleles
BASIC BIOLOGICAL SCIENCES
Biological and medical sciences
BODY
BODY AREAS
Clubfoot - epidemiology
Clubfoot - genetics
CONGENITAL MALFORMATIONS
DISEASES
Diseases of the osteoarticular system
FEET
Female
frequency
GENE MUTATIONS
genes
Genotype
HEREDITARY DISEASES
Humans
idiopathic talipes equinovarus
LEGS
LIMBS
Male
MALFORMATIONS
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
man
Medical sciences
MUTATIONS
PATHOLOGICAL CHANGES 550400 > Genetics
Pedigree
population genetics
Probability
Regression Analysis
segregation
transmission
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0002-9297
1537-6605