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Common Founder (common + founder)

Distribution by Scientific Domains
Life Sciences66%
Medical Sciences33%

Selected Abstracts

A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation

GENES, CHROMOSOMES AND CANCER, Issue 1 2005
Anders Molven
Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene. © 2005 Wiley-Liss, Inc. [source]

A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy,

HUMAN MUTATION, Issue 6 2008
Montserrat Rodríguez-Ballesteros
Abstract Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene. Cohorts of 708 Spanish, 83 Colombian, and 30 Argentinean unrelated subjects with autosomal recessive NSHI were screened for the common p.Gln829X mutation. In compound heterozygotes, the second mutant allele was identified by DNA sequencing. In total, 23 Spanish, two Colombian and two Argentinean subjects were shown to carry two mutant alleles of OTOF. Of these, one Colombian and 13 Spanish subjects presented with auditory neuropathy. In addition, a cohort of 20 unrelated subjects with a diagnosis of auditory neuropathy, from several countries, was screened for mutations in OTOF by DNA sequencing. A total of 11 of these subjects were shown to carry two mutant alleles of OTOF. In total, 18 pathogenic and four neutral novel alleles of the OTOF gene were identified. Haplotype analysis for markers close to OTOF suggests a common founder for the novel c.2905_2923delinsCTCCGAGCGCA mutation, frequently found in Argentina. Our results confirm that mutation of the OTOF gene correlates with a phenotype of prelingual, profound NSHI, and indicate that OTOF mutations are a major cause of inherited auditory neuropathy. Hum Mutat 29(6), 823,831, 2008. © 2008 Wiley-Liss, Inc. [source]

Tau (MAPT) mutation Arg406Trp presenting clinically with Alzheimer disease does not share a common founder in Western Europe,

HUMAN MUTATION, Issue 5 2003
R. Rademakers
No abstract is available for this article. [source]

Two factor XI mutations in a Chinese family with factor XI deficiency

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2003
W.Y. Au
Abstract We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713,T mutation resulting in Gln263,Term, and an exon-10 C979,A mutation resulting in Tyr351,Term. Two daughters were heterozygous for the Gln263,Term mutation and two for the Try351,Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263,Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351,Term mutation is novel. Am. J. Hematol. 74:136,138, 2003. © 2003 Wiley-Liss Inc. [source]

A shared 336 kb haplotype associated with the belt pattern in three divergent cattle breeds

ANIMAL GENETICS, Issue 3 2010
C. Drögemüller
Summary We recently mapped the belt mutation in Brown Swiss cattle to a 922 kb interval on BTA3. In this study, we analysed two additional cattle breeds with the belted phenotype: Galloway and Dutch Belted (Lakenvelder). By genotyping microsatellites in solid-coloured and belted Galloways, we confirmed that the belt mutation in Galloways is strongly associated with the same chromosomal locus as in Brown Swiss cattle. Subsequently, we analysed 36 SNPs in the belt interval in three breeds. We identified a single belt-associated haplotype for each of the analysed breeds. The three breed-specific belt haplotypes share alleles in four blocks. Three of these blocks comprise only one single or two consecutive markers, while the largest shared haplotype block encompasses nine consecutive SNPs in a 336 kb interval. The large shared haplotype across divergent breeds suggests a common mutation for the belt phenotype in all three breeds. We identified a potential candidate gene within this interval coding for the developmental transcription factor HES6. We re-sequenced the complete HES6 coding sequence in belted and solid-coloured cattle but did not find belt-associated polymorphisms. In conclusion, our data provide strong evidence in favour of a common founder for the belt phenotype in different cattle breeds and have resulted in an improved fine-mapping of the causative mutation. [source]

Deconstructing Jaco: Genetic Heritage of an Afrikaner

ANNALS OF HUMAN GENETICS, Issue 5 2007
J. M. Greeff
Summary It is often assumed that Afrikaners stem from a small number of Dutch immigrants. As a result they should be genetically homogeneous, show founder effects and be rather inbred. By disentangling my own South African pedigree, that is on average 12 generations deep, I try to quantify the genetic heritage of an Afrikaner. As much as 6% of my genes have been contributed by slaves from Africa, Madagascar and India, and a woman from China. This figure compares well to other genetic and genealogical estimates. Seventy three percent of my lineages coalesce into common founders, and I am related in excess of 10 times to 20 founder ancestors (30 times to Willem Schalk van der Merwe). Significant founder effects are thus possible. The overrepresentation of certain founder ancestors is in part explained by the fact that they had more children. This is remarkable given that they lived more than 300 years (or 12 generations) ago. DECONSTRUCT, a new program for pedigree analysis, identified 125 common ancestors in my pedigree. However, these common ancestors are so distant from myself, paths of between 16 and 25 steps in length, that my inbreeding coefficient is not unusually high (f , 0.0019). [source]