Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions
Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been...
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| Vydané v: | Annals of human genetics Ročník 80; číslo 3; s. 187 - 196 |
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| Hlavní autori: | , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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England
Wiley Subscription Services, Inc
01.05.2016
John Wiley and Sons Inc |
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| ISSN: | 0003-4800, 1469-1809, 1469-1809 |
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| Abstract | Summary
Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. |
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| AbstractList | Summary
Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome--even when completely "knocked out," do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations "as a whole" can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome-even when completely "knocked out," do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations "as a whole" can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient.Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome-even when completely "knocked out," do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations "as a whole" can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. |
| Author | Rodriguez, Santiago Gaunt, Tom R. Day, Ian N.M. Erzurumluoglu, A. Mesut Shihab, Hashem A. |
| AuthorAffiliation | 2 MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine University of Bristol Bristol UK 1 Bristol Genetic Epidemiology Laboratories (BGEL), School of Social and Community Medicine University of Bristol Bristol UK 3 Genetic Epidemiology Group, Department of Health Sciences University of Leicester Leicester UK |
| AuthorAffiliation_xml | – name: 3 Genetic Epidemiology Group, Department of Health Sciences University of Leicester Leicester UK – name: 2 MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine University of Bristol Bristol UK – name: 1 Bristol Genetic Epidemiology Laboratories (BGEL), School of Social and Community Medicine University of Bristol Bristol UK |
| Author_xml | – sequence: 1 givenname: A. Mesut surname: Erzurumluoglu fullname: Erzurumluoglu, A. Mesut organization: University of Leicester – sequence: 2 givenname: Hashem A. surname: Shihab fullname: Shihab, Hashem A. organization: University of Bristol – sequence: 3 givenname: Santiago surname: Rodriguez fullname: Rodriguez, Santiago organization: University of Bristol – sequence: 4 givenname: Tom R. surname: Gaunt fullname: Gaunt, Tom R. organization: University of Bristol – sequence: 5 givenname: Ian N.M. surname: Day fullname: Day, Ian N.M. organization: University of Bristol |
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| Keywords | complex disease gene function Consanguineous populations Mendelian disease autozygosity |
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Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF)... Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations... Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF)... |
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| SubjectTerms | autozygosity Chromosome Mapping complex disease Consanguineous populations Consanguinity gene function Gene Silencing Genes Genetics, Population Genome, Human Genomes Heterozygote Homozygote Humans Mendelian disease Mutation Phenotype Review |
| Title | Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions |
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