Article: DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: Standardization of molecular investigations of genetic diseases due to consanguinity

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TitleDNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: Standardization of molecular investigations of genetic diseases due to consanguinity
AuthorsLam, CW2
Tong, SF2
Wong, K4
Luo, YF4
Tang, HY3
Ha, SY1
Chan, MHM2
Issue Date2007
PublisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htm
CitationJournal Of Human Genetics, 2007, v. 52 n. 1, p. 98-101 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10038-006-0075-4
AbstractMalignant osteopetrosis, a severe disease causing early infantile death in humans, is caused by mutations in the TCIRG1, CLCN7, or OSTM1 genes. We have established the molecular basis of malignant osteopetrosis in a Chinese family by means of whole-genome scans based on high-density single-nucleotide polymorphism (SNP) microarrays. Because the parents were consanguineous, the disease-causing locus should be located in an autozygous chromosomal region. Mapping revealed that among the three possible causal loci, only the CLCN7 gene was located in an autozygous region. Mutational analysis of the CLCN7 gene showed that the proband was homozygous for a novel missense mutation, p.I261F. p.I261 is located in helix F of the chloride channel, near a critical site for gating of the channel. This mapping study prepares the ground for future mutation studies by decreasing the burden of completely sequencing all possible loci for this disease. This approach can be used to standardize molecular investigations of genetic diseases due to consanguinity to a whole-genome scan and subsequent sequencing of the mapped disease gene. © 2006 The Japan Society of Human Genetics and Springer.
ISSN1434-5161
2011 Impact Factor: 2.57
2011 SCImago Journal Rankings: 0.317
DOIhttp://dx.doi.org/10.1007/s10038-006-0075-4
ISI Accession Number IDWOS:000242853400012
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLam, CW
dc.contributor.authorTong, SF
dc.contributor.authorWong, K
dc.contributor.authorLuo, YF
dc.contributor.authorTang, HY
dc.contributor.authorHa, SY
dc.contributor.authorChan, MHM
dc.date.accessioned2012-05-29T06:13:18Z
dc.date.available2012-05-29T06:13:18Z
dc.date.issued2007
dc.description.abstractMalignant osteopetrosis, a severe disease causing early infantile death in humans, is caused by mutations in the TCIRG1, CLCN7, or OSTM1 genes. We have established the molecular basis of malignant osteopetrosis in a Chinese family by means of whole-genome scans based on high-density single-nucleotide polymorphism (SNP) microarrays. Because the parents were consanguineous, the disease-causing locus should be located in an autozygous chromosomal region. Mapping revealed that among the three possible causal loci, only the CLCN7 gene was located in an autozygous region. Mutational analysis of the CLCN7 gene showed that the proband was homozygous for a novel missense mutation, p.I261F. p.I261 is located in helix F of the chloride channel, near a critical site for gating of the channel. This mapping study prepares the ground for future mutation studies by decreasing the burden of completely sequencing all possible loci for this disease. This approach can be used to standardize molecular investigations of genetic diseases due to consanguinity to a whole-genome scan and subsequent sequencing of the mapped disease gene. © 2006 The Japan Society of Human Genetics and Springer.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Human Genetics, 2007, v. 52 n. 1, p. 98-101 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10038-006-0075-4
dc.identifier.citeulike1037942
dc.identifier.doihttp://dx.doi.org/10.1007/s10038-006-0075-4
dc.identifier.epage101
dc.identifier.isiWOS:000242853400012
dc.identifier.issn1434-5161
2011 Impact Factor: 2.57
2011 SCImago Journal Rankings: 0.317
dc.identifier.issue1
dc.identifier.pmid17033731
dc.identifier.scopuseid_2-s2.0-33845903823
dc.identifier.spage98
dc.identifier.urihttp://hdl.handle.net/10722/148497
dc.identifier.volume52
dc.languageeng
dc.publisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htm
dc.publisher.placeJapan
dc.relation.ispartofJournal of Human Genetics
dc.relation.referencesReferences in Scopus
dc.subject.meshAsian Continental Ancestry Group
dc.subject.meshBase Sequence
dc.subject.meshChloride Channels - Genetics
dc.subject.meshConsanguinity
dc.subject.meshDna Mutational Analysis - Methods
dc.subject.meshFemale
dc.subject.meshGenome, Human
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMembrane Proteins - Genetics
dc.subject.meshMolecular Sequence Data
dc.subject.meshOligonucleotide Array Sequence Analysis - Methods - Standards
dc.subject.meshOsteopetrosis - Diagnosis - Genetics
dc.subject.meshPedigree
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshUbiquitin-Protein Ligases - Genetics
dc.subject.meshVacuolar Proton-Translocating Atpases - Genetics
dc.titleDNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: Standardization of molecular investigations of genetic diseases due to consanguinity
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Prince of Wales Hospital Hong Kong
  3. Tsan Yuk Hospital
  4. Centro Hospitalar Conde de S. Januário (CHCSJ)