TY - JOUR
T1 - Effect of within-strain sample size on GTL detection and mapping using recombinant inbred mouse strains
AU - Belknap, J. K.
N1 - Funding Information:
This work was supported by a VA Merit Review Program from the Department of Veterans Affairs and by NIH Grants AA06243, AA10760, DA05228, and DA10913.
PY - 1998
Y1 - 1998
N2 - Increasing the number of mice used to calculate recombinant inbred (RJ) strain means increases the accuracy of determining the phenotype associated with each genotype (strain), which in turn enhances quantitative trait locus (QTL) detection and mapping. The purpose of this paper is to examine quantitatively the effect of within-strain sample size (n) on additive QTL mapping efficiency and to make comparisons with F2 and backcross (BC) populations, where each genotype is represented by only a single mouse. When 25 RI strains are used, the estimated equivalent number of F2 mice yielding the same power to detect Qtls varies inversely as a function of the heritability of the trait in the RI population (h(RI)2). For example, testing 25 strains with n = 10 per strain is approximately equivalent to 160 F2 mice when h(RI)2 = 0.2, but only 55 when h(RI)2 = 0.6. While increasing n is always beneficial, the gain in power as n increases is greatest when h(RI)2 is low and is much diminished at high h(RI)2 values. Thus, when h(RI)2 is high, there is little advantage of large n, even when n approaches infinity. A cost analysis suggested that RI populations are more cost- effective than conventional selectively genotyped F2 populations at h(RI)2 values likely to be seen in behavioral studies. However, with DNA pooling, this advantage is greatly reduced and may be reversed depending on the values of h(RI)2 and n.
AB - Increasing the number of mice used to calculate recombinant inbred (RJ) strain means increases the accuracy of determining the phenotype associated with each genotype (strain), which in turn enhances quantitative trait locus (QTL) detection and mapping. The purpose of this paper is to examine quantitatively the effect of within-strain sample size (n) on additive QTL mapping efficiency and to make comparisons with F2 and backcross (BC) populations, where each genotype is represented by only a single mouse. When 25 RI strains are used, the estimated equivalent number of F2 mice yielding the same power to detect Qtls varies inversely as a function of the heritability of the trait in the RI population (h(RI)2). For example, testing 25 strains with n = 10 per strain is approximately equivalent to 160 F2 mice when h(RI)2 = 0.2, but only 55 when h(RI)2 = 0.6. While increasing n is always beneficial, the gain in power as n increases is greatest when h(RI)2 is low and is much diminished at high h(RI)2 values. Thus, when h(RI)2 is high, there is little advantage of large n, even when n approaches infinity. A cost analysis suggested that RI populations are more cost- effective than conventional selectively genotyped F2 populations at h(RI)2 values likely to be seen in behavioral studies. However, with DNA pooling, this advantage is greatly reduced and may be reversed depending on the values of h(RI)2 and n.
KW - Chromosome mapping
KW - Mouse
KW - Quantitative genetics
KW - Quantitative trait locus
KW - Recombinant inbred strai
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U2 - 10.1023/A:1021404714631
DO - 10.1023/A:1021404714631
M3 - Article
C2 - 9573644
AN - SCOPUS:0031914691
SN - 0001-8244
VL - 28
SP - 29
EP - 38
JO - Behavior genetics
JF - Behavior genetics
IS - 1
ER -