MULTIPOINT GENETIC-MAPPING OF QUANTITATIVE TRAIT LOCI USING A VARIABLE NUMBER OF SIBS PER FAMILY

We present a multipoint algorithm to map quantitative trait loci (QTLs ) using families from outbred populations with a variable number of si bs. The algorithm uses information from all markers on a chromosome si multaneously to extract information of QTL segregation. A previous mul tipoint method (Kruglyak & Lander (1995) American Journal of Human Gen etics 57, 439-454) extracts information using a hidden Markov model. H owever, this method is restricted to small families (<10 sibs). We pre sent an approximate hidden Markov model approach that can handle large sibships while retaining similar efficiency to the previous method. C omputer simulations support the notion that data sampled from a small number of large families provide more power than data obtained from a large number of small families, under the constraint that the total nu mber of individuals for the two schemes is the same. This is further r eflected in simulations with variable family sizes, where variance in family size improves the statistical power of QTL detection relative t o a constant size control.