Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

N. Limaye; K. A. Belobrajdic; A. E. Wandstrat; F. Bonhomme; S. V. Edwards; E. K. Wakeland

doi:10.1038/sj.gene.6364446

Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

N. Limaye, K. A. Belobrajdic, A. E. Wandstrat, F. Bonhomme, S. V. Edwards, E. K. Wakeland

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

Original language	English (US)
Pages (from-to)	61-68
Number of pages	8
Journal	Genes and Immunity
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/sj.gene.6364446
State	Published - Jan 2008

ASJC Scopus subject areas

Immunology
Genetics
Genetics(clinical)

Access to Document

10.1038/sj.gene.6364446

Cite this

@article{a1c62a7b99fc4e72a1ee5a8f1d0e56c4,

title = "Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations",

abstract = "The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.",

author = "N. Limaye and Belobrajdic, {K. A.} and Wandstrat, {A. E.} and F. Bonhomme and Edwards, {S. V.} and Wakeland, {E. K.}",

note = "Funding Information: Support for these studies was provided by grants from the National Institute of Allergy and Infectious Disease to EKW. NL and KB were supported by NIH training grant no. NIH T32 AI 005284. FB was supported by ISEM 2007-084.",

year = "2008",

month = jan,

doi = "10.1038/sj.gene.6364446",

language = "English (US)",

volume = "9",

pages = "61--68",

journal = "Genes and Immunity",

issn = "1466-4879",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

AU - Limaye, N.

AU - Belobrajdic, K. A.

AU - Wandstrat, A. E.

AU - Bonhomme, F.

AU - Edwards, S. V.

AU - Wakeland, E. K.

N1 - Funding Information: Support for these studies was provided by grants from the National Institute of Allergy and Infectious Disease to EKW. NL and KB were supported by NIH training grant no. NIH T32 AI 005284. FB was supported by ISEM 2007-084.

PY - 2008/1

Y1 - 2008/1

N2 - The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

AB - The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

UR - http://www.scopus.com/inward/record.url?scp=38549106554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549106554&partnerID=8YFLogxK

U2 - 10.1038/sj.gene.6364446

DO - 10.1038/sj.gene.6364446

M3 - Article

C2 - 18094711

AN - SCOPUS:38549106554

SN - 1466-4879

VL - 9

SP - 61

EP - 68

JO - Genes and Immunity

JF - Genes and Immunity

IS - 1

ER -

Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this