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Rapid gene identification in a Chinese osteopetrosis family by whole exome sequencing
- Source :
- Gene. 516(2)
- Publication Year :
- 2012
-
Abstract
- Osteopetrosis is a rare genetically heterogeneous disorder of bone metabolism characterized by increased skeleton density. In the past, standard methods for genetic diagnosis of osteopetrosis have primarily been performed by candidate gene screening and positional cloning. However, these methods are time and labor consumptive; and the genetic basis of approximately 30% of the cases is yet to be elucidated. Here, we employed whole exome sequencing of two affected individuals from an osteopetrosis family to identify a candidate mutation in CLCN7 (Y99C). It was identified from a total of 1757 and 1728 genetic variations found in either patient, which were then distilled using filtering strategies and confirmed using Sanger sequencing. We identified this mutation in six family members, while not in population matched controls. This mutation was previously found in osteopetrosis patients by other researchers. Our evolutionary analysis also indicated that it is under extremely high selective pressure, and is likely to be critical for the correct function of ClC-7, and thus is likely to be the responsible cause of disease. Collectively, our data further indicated that mutation (Y99C) may be a cause of osteopetrosis, and highlights the use of whole exome sequencing as a valuable approach to identifying disease mutations in a cost and time efficient manner.
- Subjects :
- Adult
Male
Candidate gene
Time Factors
Positional cloning
symbols.namesake
Young Adult
Asian People
Genetics
medicine
Humans
Exome
Family
Exome sequencing
Genetic Association Studies
Sanger sequencing
biology
Genetic heterogeneity
High-Throughput Nucleotide Sequencing
Osteopetrosis
General Medicine
Middle Aged
medicine.disease
Pedigree
Child, Preschool
Mutation (genetic algorithm)
symbols
biology.protein
Female
CLCN7
Subjects
Details
- ISSN :
- 18790038
- Volume :
- 516
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....65fdb465892f6968b8ebad42869bf6d3