Development of congenics for hypnotic sensitivity to ethanol by QTL-marker-assisted counter selection

Development of congenics for hypnotic sensitivity to ethanol by QTL-marker-assisted counter... Mouse strains congenic for individual quantitative trait loci (QTLs) conferring hypnotic sensitivity to ethanol were constructed by backcrossing genotypically selected ILS × ISS N2 individuals to either inbred Long Sleep (ILS) or inbred Short Sleep (ISS) mice. We used a novel ``speed congenic'' approach in which N2 mice were genotyped for markers flanking each of the five originally identified QTLs. Genotypic selection for ISS regions at four of the five QTLs, and for ILS/ISS at the fifth QTL, allowed rapid fixation of the genetic background. We call this strategy ``QTL-Marker-Assisted Counter Selection'' or QMACS. By the N4 generation, phenotypic assessments showed that in some sublines the QTL had not been captured; these sublines were discarded and positive lines split to create new replicate sublines. One QTL, on Chromosome (Chr) 8, was not confirmed. At the N8, virtually all sublines on the remaining QTLs retained the phenotypic difference between heterozygotes and ISS homozygotes. Small numbers of interim congenics were produced at the N6 and later generations in which the ILS QTL was made homozygous on the ISS background; as expected, these congenic mice showed an increased sleep time. For later backcrosses (after the N4), the parents were selected on the basis of phenotype as well as genotype. The parent-offspring correlation over all QTLs was significant, supporting the use of phenotypic selection in congenic construction. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Development of congenics for hypnotic sensitivity to ethanol by QTL-marker-assisted counter selection

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Publisher
Springer Journals
Copyright
Copyright © 1998 by Springer-Verlag New York Inc.
Subject
Life Sciences; Cell Biology; Animal Genetics and Genomics; Human Genetics
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s003359900908
Publisher site
See Article on Publisher Site

Abstract

Mouse strains congenic for individual quantitative trait loci (QTLs) conferring hypnotic sensitivity to ethanol were constructed by backcrossing genotypically selected ILS × ISS N2 individuals to either inbred Long Sleep (ILS) or inbred Short Sleep (ISS) mice. We used a novel ``speed congenic'' approach in which N2 mice were genotyped for markers flanking each of the five originally identified QTLs. Genotypic selection for ISS regions at four of the five QTLs, and for ILS/ISS at the fifth QTL, allowed rapid fixation of the genetic background. We call this strategy ``QTL-Marker-Assisted Counter Selection'' or QMACS. By the N4 generation, phenotypic assessments showed that in some sublines the QTL had not been captured; these sublines were discarded and positive lines split to create new replicate sublines. One QTL, on Chromosome (Chr) 8, was not confirmed. At the N8, virtually all sublines on the remaining QTLs retained the phenotypic difference between heterozygotes and ISS homozygotes. Small numbers of interim congenics were produced at the N6 and later generations in which the ILS QTL was made homozygous on the ISS background; as expected, these congenic mice showed an increased sleep time. For later backcrosses (after the N4), the parents were selected on the basis of phenotype as well as genotype. The parent-offspring correlation over all QTLs was significant, supporting the use of phenotypic selection in congenic construction.

Journal

Mammalian GenomeSpringer Journals

Published: Dec 1, 1998

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