Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice

T. N. Ferraro, G. G. Smith, D. Ballard, H. Zhao, C. L. Schwebel, A. Gupta, E. F. Rappaport, S. E. Ruiz, F. W. Lohoff, G. A. Doyle, W. H. Berrettini, R. J. Buono

Research output: Contribution to journalArticle

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Abstract

We mapped the quantitative trait loci (QTL) that contribute to the robust difference in maximal electroshock seizure threshold (MEST) between C57BLKS/J (BKS) and C57BL10S/J (B10S) mice. BKS, B10S, BKS × B10S F1 and BKS × B10S F2 intercross mice were tested for MEST at 8-9 weeks of age. Results of F2 testing showed that, in this cross, MEST is a continuously distributed trait determined by polygenic inheritance. Mice from the extremes of the trait distribution were genotyped using microarray technology. MEST correlated significantly with body weight and sex; however, because of the high correlation between these factors, the QTL mapping was conditioned on sex alone. A sequential series of statistical analyses was used to map QTLs including single-point, multipoint and multilocus methods. Two QTLs reached genome-wide levels of significance based upon an empirically determined permutation threshold: chromosome 6 (LOD = 6.0 at ~69 cM) and chromosome 8 (LOD = 5.7 at ~27 cM). Two additional QTLs were retained in a multilocus regression model: chromosome 3 (LOD = 2.1 at ~68 cM) and chromosome 5 (LOD = 2.7 at ~73 cM). Together the four QTLs explain one third of the total phenotypic variance in the mapping population. Lack of overlap between the major MEST QTLs mapped here in BKS and B10S mice and those mapped previously in C57BL/6J and DBA/2J mice (strains that are closely related to BKS and B10S) suggest that BKS and B10S represent a new polygenic mouse model for investigating susceptibility to seizures.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalGenes, Brain and Behavior
Volume10
Issue number3
DOIs
StatePublished - Apr 1 2011

Fingerprint

Quantitative Trait Loci
Electroshock
Inbred C57BL Mouse
Seizures
Multifactorial Inheritance
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 5
Inbred DBA Mouse
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 3
Body Weight
Genome
Technology
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Ferraro, T. N. ; Smith, G. G. ; Ballard, D. ; Zhao, H. ; Schwebel, C. L. ; Gupta, A. ; Rappaport, E. F. ; Ruiz, S. E. ; Lohoff, F. W. ; Doyle, G. A. ; Berrettini, W. H. ; Buono, R. J. / Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice. In: Genes, Brain and Behavior. 2011 ; Vol. 10, No. 3. pp. 309-315.
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abstract = "We mapped the quantitative trait loci (QTL) that contribute to the robust difference in maximal electroshock seizure threshold (MEST) between C57BLKS/J (BKS) and C57BL10S/J (B10S) mice. BKS, B10S, BKS × B10S F1 and BKS × B10S F2 intercross mice were tested for MEST at 8-9 weeks of age. Results of F2 testing showed that, in this cross, MEST is a continuously distributed trait determined by polygenic inheritance. Mice from the extremes of the trait distribution were genotyped using microarray technology. MEST correlated significantly with body weight and sex; however, because of the high correlation between these factors, the QTL mapping was conditioned on sex alone. A sequential series of statistical analyses was used to map QTLs including single-point, multipoint and multilocus methods. Two QTLs reached genome-wide levels of significance based upon an empirically determined permutation threshold: chromosome 6 (LOD = 6.0 at ~69 cM) and chromosome 8 (LOD = 5.7 at ~27 cM). Two additional QTLs were retained in a multilocus regression model: chromosome 3 (LOD = 2.1 at ~68 cM) and chromosome 5 (LOD = 2.7 at ~73 cM). Together the four QTLs explain one third of the total phenotypic variance in the mapping population. Lack of overlap between the major MEST QTLs mapped here in BKS and B10S mice and those mapped previously in C57BL/6J and DBA/2J mice (strains that are closely related to BKS and B10S) suggest that BKS and B10S represent a new polygenic mouse model for investigating susceptibility to seizures.",
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Ferraro, TN, Smith, GG, Ballard, D, Zhao, H, Schwebel, CL, Gupta, A, Rappaport, EF, Ruiz, SE, Lohoff, FW, Doyle, GA, Berrettini, WH & Buono, RJ 2011, 'Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice', Genes, Brain and Behavior, vol. 10, no. 3, pp. 309-315. https://doi.org/10.1111/j.1601-183X.2010.00668.x

Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice. / Ferraro, T. N.; Smith, G. G.; Ballard, D.; Zhao, H.; Schwebel, C. L.; Gupta, A.; Rappaport, E. F.; Ruiz, S. E.; Lohoff, F. W.; Doyle, G. A.; Berrettini, W. H.; Buono, R. J.

In: Genes, Brain and Behavior, Vol. 10, No. 3, 01.04.2011, p. 309-315.

Research output: Contribution to journalArticle

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T1 - Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice

AU - Ferraro, T. N.

AU - Smith, G. G.

AU - Ballard, D.

AU - Zhao, H.

AU - Schwebel, C. L.

AU - Gupta, A.

AU - Rappaport, E. F.

AU - Ruiz, S. E.

AU - Lohoff, F. W.

AU - Doyle, G. A.

AU - Berrettini, W. H.

AU - Buono, R. J.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - We mapped the quantitative trait loci (QTL) that contribute to the robust difference in maximal electroshock seizure threshold (MEST) between C57BLKS/J (BKS) and C57BL10S/J (B10S) mice. BKS, B10S, BKS × B10S F1 and BKS × B10S F2 intercross mice were tested for MEST at 8-9 weeks of age. Results of F2 testing showed that, in this cross, MEST is a continuously distributed trait determined by polygenic inheritance. Mice from the extremes of the trait distribution were genotyped using microarray technology. MEST correlated significantly with body weight and sex; however, because of the high correlation between these factors, the QTL mapping was conditioned on sex alone. A sequential series of statistical analyses was used to map QTLs including single-point, multipoint and multilocus methods. Two QTLs reached genome-wide levels of significance based upon an empirically determined permutation threshold: chromosome 6 (LOD = 6.0 at ~69 cM) and chromosome 8 (LOD = 5.7 at ~27 cM). Two additional QTLs were retained in a multilocus regression model: chromosome 3 (LOD = 2.1 at ~68 cM) and chromosome 5 (LOD = 2.7 at ~73 cM). Together the four QTLs explain one third of the total phenotypic variance in the mapping population. Lack of overlap between the major MEST QTLs mapped here in BKS and B10S mice and those mapped previously in C57BL/6J and DBA/2J mice (strains that are closely related to BKS and B10S) suggest that BKS and B10S represent a new polygenic mouse model for investigating susceptibility to seizures.

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