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Fine mapping analysis confirms and strengthens linkage of four chromosomal regions in familial hypospadias
- Source :
- European Journal of Human Genetics, 23, 516-22, European Journal of Human Genetics, 23, 4, pp. 516-22
- Publication Year :
- 2015
-
Abstract
- Item does not contain fulltext Hypospadias is a common male genital malformation and is regarded as a complex disease affected by multiple genetic as well as environmental factors. In a previous genome-wide scan for familial hypospadias, we reported suggestive linkage in nine chromosomal regions. We have extended this analysis by including new families and additional markers using non-parametric linkage. The fine mapping analysis displayed an increased LOD score on chromosome 8q24.1 and 10p15 in altogether 82 families. On chromosome 10p15, with the highest LOD score, we further studied AKR1C2, AKR1C3 and AKR1C4 involved in steroid metabolism, as well as KLF6 expressed in preputial tissue from hypospadias patients. Mutation analysis of the AKR1C3 gene showed a new mutation, c.643G>A (p.(Ala215Thr)), in a boy with penile hypospadias. This mutation is predicted to have an impact on protein function and structure and was not found in controls. Altogether, we homed in on four chromosomal regions likely to harbor genes for hypospadias. Future studies will aim for studying regulatory sequence variants in these regions.
- Subjects :
- Male
medicine.medical_specialty
3-Hydroxysteroid Dehydrogenases
Genotype
Genotyping Techniques
Kruppel-Like Transcription Factors
Biology
Polymorphism, Single Nucleotide
Article
White People
Asian People
Gene Frequency
Genetic linkage
Proto-Oncogene Proteins
Genetics
medicine
Kruppel-Like Factor 6
Humans
Genetic Predisposition to Disease
Allele frequency
Genetics (clinical)
Genetic Association Studies
Hypospadias
Chromosomes, Human, Pair 10
Metabolic Disorders Radboud Institute for Health Sciences [Radboudumc 6]
Cytogenetics
Aldo-Keto Reductase Family 1 Member C3
Hydroxysteroid Dehydrogenases
Chromosome
Chromosome Mapping
Exons
medicine.disease
Human genetics
Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10]
Gene Expression Regulation
Case-Control Studies
Mutation (genetic algorithm)
Hydroxyprostaglandin Dehydrogenases
Medical genetics
Renal disorders Radboud Institute for Health Sciences [Radboudumc 11]
Lod Score
Oxidoreductases
Chromosomes, Human, Pair 8
Microsatellite Repeats
Subjects
Details
- ISSN :
- 10184813
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....aad037de4f83457d8a98633b81a56f95