Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies
Abstract Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). E...
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Online Access: | http://dx.doi.org/10.1093/genetics/156.3.1259 https://academic.oup.com/genetics/article-pdf/156/3/1259/42033863/genetics1259.pdf |
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croxfordunivpr:10.1093/genetics/156.3.1259 2024-09-15T18:16:16+00:00 Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies Templeton, Alan R Weiss, Kenneth M Nickerson, Deborah A Boerwinkle, Eric Sing, Charles F 2000 http://dx.doi.org/10.1093/genetics/156.3.1259 https://academic.oup.com/genetics/article-pdf/156/3/1259/42033863/genetics1259.pdf en eng Oxford University Press (OUP) https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model Genetics volume 156, issue 3, page 1259-1275 ISSN 1943-2631 journal-article 2000 croxfordunivpr https://doi.org/10.1093/genetics/156.3.1259 2024-08-05T04:34:14Z Abstract Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3′ region should have general utility in most human populations, but the 5′ SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region. Article in Journal/Newspaper karelia* Oxford University Press Genetics 156 3 1259 1275 |
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Oxford University Press |
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English |
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Abstract Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3′ region should have general utility in most human populations, but the 5′ SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region. |
format |
Article in Journal/Newspaper |
author |
Templeton, Alan R Weiss, Kenneth M Nickerson, Deborah A Boerwinkle, Eric Sing, Charles F |
spellingShingle |
Templeton, Alan R Weiss, Kenneth M Nickerson, Deborah A Boerwinkle, Eric Sing, Charles F Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
author_facet |
Templeton, Alan R Weiss, Kenneth M Nickerson, Deborah A Boerwinkle, Eric Sing, Charles F |
author_sort |
Templeton, Alan R |
title |
Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
title_short |
Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
title_full |
Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
title_fullStr |
Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
title_full_unstemmed |
Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies |
title_sort |
cladistic structure within the human lipoprotein lipase gene and its implications for phenotypic association studies |
publisher |
Oxford University Press (OUP) |
publishDate |
2000 |
url |
http://dx.doi.org/10.1093/genetics/156.3.1259 https://academic.oup.com/genetics/article-pdf/156/3/1259/42033863/genetics1259.pdf |
genre |
karelia* |
genre_facet |
karelia* |
op_source |
Genetics volume 156, issue 3, page 1259-1275 ISSN 1943-2631 |
op_rights |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
op_doi |
https://doi.org/10.1093/genetics/156.3.1259 |
container_title |
Genetics |
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156 |
container_issue |
3 |
container_start_page |
1259 |
op_container_end_page |
1275 |
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1810454273287258112 |