Analysing complex genetic traits with chromosome substitution strains

Joseph H. Nadeau; Jonathan B. Singer; Angabin Matin; Eric S. Lander

doi:10.1038/73427

Analysing complex genetic traits with chromosome substitution strains

Joseph H. Nadeau, Jonathan B. Singer, Angabin Matin, Eric S. Lander

Genetics

Research output: Contribution to journal › Review article › peer-review

394 Scopus citations

Abstract

Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.

Original language	English (US)
Pages (from-to)	221-225
Number of pages	5
Journal	Nature Genetics
Volume	24
Issue number	3
DOIs	https://doi.org/10.1038/73427
State	Published - Mar 2000

ASJC Scopus subject areas

Genetics

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title = "Analysing complex genetic traits with chromosome substitution strains",

abstract = "Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.",

author = "Nadeau, {Joseph H.} and Singer, {Jonathan B.} and Angabin Matin and Lander, {Eric S.}",

note = "Funding Information: J.B.S. was supported by NHGRI grant F32 HG00195. This work was supported by NIH grant RR12305 and CA75056 to J.H.N., a grant from the Keck Foundation to the Department of Genetics, Case Western Reserve University School of Medicine, a grant from the Howard Hughes Medical Institute to Case Western Reserve University School of Medicine and grants from the NIH to E.S.L.",

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doi = "10.1038/73427",

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AU - Nadeau, Joseph H.

AU - Singer, Jonathan B.

AU - Matin, Angabin

AU - Lander, Eric S.

N1 - Funding Information: J.B.S. was supported by NHGRI grant F32 HG00195. This work was supported by NIH grant RR12305 and CA75056 to J.H.N., a grant from the Keck Foundation to the Department of Genetics, Case Western Reserve University School of Medicine, a grant from the Howard Hughes Medical Institute to Case Western Reserve University School of Medicine and grants from the NIH to E.S.L.

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Y1 - 2000/3

N2 - Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.

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Analysing complex genetic traits with chromosome substitution strains

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