Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T&gt;A/c.130T&gt;A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer

Hansen, Thomas V.O.; Jønson, Lars; Albrechtsen, Anders; Steffensen, Ane Y.; Bergsten, Eva; Myrhøj, T; Ejlertsen, Bent; Nielsen, Finn C.

doi:10.1007/s10549-010-0909-9

Cited by 10 publications

(17 citation statements)

References 28 publications

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“…In this study a disease-causing point mutation in the BRCA1 gene was identified in a Greenlandic Inuit with ovarian cancer (Hansen et al 2010). It was the first report of this specific point mutation in the Greenlandic Inuit population, but the same point mutation had previously been observed among four Danes with breast and/or ovarian cancer.…”

Section: Applications To Analyses Of Disease-related Mutationssupporting

confidence: 53%

“…The first data set consists of five patients with breast and/or ovarian cancer, four Danes and one Greenlandic Inuit. These individuals are all heterozygous for a recently identified mutation in their BRCA1 gene on chromosome 17 (Hansen et al 2010). Except for two of the individuals that have a coancestry coefficient of 0.107, the individuals are seemingly unrelated (the remaining coancestry coefficients are all lower than 0.014).…”

Section: Real Test Datamentioning

confidence: 99%

“…The base calling was performed using the BRLMM algorithm (Affymetrix 2006). The first data set was genotyped and called by Hansen et al (2010), the second by Affymetrix.…”

Section: Real Test Datamentioning

confidence: 99%

“…To illustrate the potential of the MCMC method for analyses of disease-related questions, we applied it to SNP chip data from a recent study by Hansen et al (2010). In this study a disease-causing point mutation in the BRCA1 gene was identified in a Greenlandic Inuit with ovarian cancer (Hansen et al 2010).…”

Section: Applications To Analyses Of Disease-related Mutationsmentioning

confidence: 99%

“…It was the first report of this specific point mutation in the Greenlandic Inuit population, but the same point mutation had previously been observed among four Danes with breast and/or ovarian cancer. By use of pairwise IBD analysis with Relate, Hansen et al (2010) investigated whether or not all five cancer patients share the allele IBD and found it very likely that they do, and thus, that their mutations are all caused by a single founder mutation. As a consequence, the authors recommended that the current approach to genetic screening of Greenlandic Inuit families with breast and/or ovarian cancer should be changed.…”

Section: Applications To Analyses Of Disease-related Mutationsmentioning

confidence: 99%

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A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

Moltke¹,

Albrechtsen²,

Hansen³

et al. 2011

Genome Res.

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All individuals in a finite population are related if traced back long enough and will, therefore, share regions of their genomes identical by descent (IBD). Detection of such regions has several important applications-from answering questions about human evolution to locating regions in the human genome containing disease-causing variants. However, IBD regions can be difficult to detect, especially in the common case where no pedigree information is available. In particular, all existing non-pedigree based methods can only infer IBD sharing between two individuals. Here, we present a new Markov Chain Monte Carlo method for detection of IBD regions, which does not rely on any pedigree information. It is based on a probabilistic model applicable to unphased SNP data. It can take inbreeding, allele frequencies, genotyping errors, and genomic distances into account. And most importantly, it can simultaneously infer IBD sharing among multiple individuals. Through simulations, we show that the simultaneous modeling of multiple individuals makes the method more powerful and accurate than several other non-pedigree based methods. We illustrate the potential of the method by applying it to data from individuals with breast and/or ovarian cancer, and show that a known disease-causing mutation can be mapped to a 2.2-Mb region using SNP data from only five seemingly unrelated affected individuals. This would not be possible using classical linkage mapping or association mapping.[Supplemental material is available for this article. The MCMC software is freely available at http://people.binf.ku.dk/ida/ Software/MCMC_IBDfinder/.] Identity by descent (IBD) is a fundamental concept in genetics. Two or more individuals share a region of their genomes IBD if they have identical nucleotide sequences in this region due to common ancestry. The concept of IBD has existed for a long time. It was introduced in the 1940s (Malecot 1946(Malecot , 1948 and has since then received attention within a number of fields of genetic research, ranging from forensic genetics (Evett and Weir 1998) to molecular ecology (Thompson 1975;Queller and Goodnight 1989;Ritland 1996;Lynch and Ritland 1999). But, most importantly, during the last several decades it has played an essential role within the field of human disease mapping. Until the beginning of this century, the main focus within this field was the development of methods for analyzing data from families with known pedigrees (Elston and Stewart 1971;Ott 1974;Cannings et al. 1978;Lander and Green 1987;Kruglyak et al. 1996;Abecasis et al. 2002). However, the concept of IBD has recently received renewed attention in the context of genomic data without any external pedigree information (Purcell et al. 2007;Browning 2008;Thompson 2008;Albrechtsen et al. 2009Albrechtsen et al. , 2010Gusev et al. 2009;Browning and Browning 2010).There are a number of different definitions of IBD in different contexts. In most human single nucleotide polymorphism (SNP) data, each SNP is caused by a single mutation. Therefo...

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Section: Applications To Analyses Of Disease-related Mutationssupporting

confidence: 53%

Section: Real Test Datamentioning

confidence: 99%

“…The base calling was performed using the BRLMM algorithm (Affymetrix 2006). The first data set was genotyped and called by Hansen et al (2010), the second by Affymetrix.…”

Section: Real Test Datamentioning

confidence: 99%

Section: Applications To Analyses Of Disease-related Mutationsmentioning

confidence: 99%

Section: Applications To Analyses Of Disease-related Mutationsmentioning

confidence: 99%

See 3 more Smart Citations

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

Moltke¹,

Albrechtsen²,

Hansen³

et al. 2011

Genome Res.

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Identification of six pathogenic RAD51C mutations via mutational screening of 1228 Danish individuals with increased risk of hereditary breast and/or ovarian cancer

Jønson

Ahlborn

Steffensen

et al. 2016

Breast Cancer Res Treat

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Germ-line mutations in the RAD51C gene have recently been identified in families with breast and ovarian cancer and have been associated with an increased risk of ovarian cancer. In this study, we describe the frequency of pathogenic RAD51C mutations identified in Danish breast and/or ovarian cancer families. We screened the RAD51C gene in 1228 Danish hereditary breast and/or ovarian cancer families by next-generation sequencing analysis. The frequency of the identified variants was examined in the exome sequencing project database and in data from 2000 Danish exomes and the presumed significance of missense and intronic variants was predicted by in silico analysis. We identified six families with a pathogenic mutation in RAD51C, including three frameshift mutations, one nonsense mutation, and 2 missense mutations. Overall, pathogenic RAD51C mutations were identified in 0.5 % of Danish families with increased risk of hereditary breast and/or ovarian cancer. Moreover, we identified 24 additional RAD51C variants of which 14 have not been previously reported in the literature. In this study, we determine the prevalence of RAD51C mutations in Danish breast and/or ovarian cancer families. We identified six pathogenic RAD51C mutations as well as 23 variants of uncertain clinical significance and one benign variant. Together, the study extends our knowledge of the RAD51C mutation spectrum and supports that RAD51C should be included in gene panel testing of individuals with high risk of breast and ovarian cancer.

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Founder vs. non-founder BRCA1/2 pathogenic alleles: the analysis of Belarusian breast and ovarian cancer patients and review of other studies on ethnically homogenous populations

et al. 2022

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Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer

Cited by 10 publications

References 28 publications

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

Identification of six pathogenic RAD51C mutations via mutational screening of 1228 Danish individuals with increased risk of hereditary breast and/or ovarian cancer

Founder vs. non-founder BRCA1/2 pathogenic alleles: the analysis of Belarusian breast and ovarian cancer patients and review of other studies on ethnically homogenous populations

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