Classic Weinstein: Tetrad analysis, genetic variation and achiasmate segregation in Drosophila and humans

A maximum-likelihood method for the estimation of tetrad frequencies from s ingle-spore data is presented. The multilocus exchange with interference an d viability (MEIV) model incorporates a clearly defined model of exchange, interference, and viability whose parameters define a multinomial distribut ion for single-spore data. Maximum-likelihood analysis of the MEIV model (M EIVLA) allows point estimation of tetrad frequencies and determination of c onfidence intervals. We employ MEIVLA to determine tetrad frequencies among 15 X chromosomes sampled at random from Drosophila melanogaster natural po pulations in Africa and North America. Significant variation in the frequen cy of nonexchange, or Eo tetrads, is observed within both natural populatio ns. Because most nondisjunction arises from Eo tetrads, this observation is quite unexpected given both the prevalence and the deleterious consequence s of nondisjunction in D. melanogaster. Use of MEIVLA is also demonstrated by reanalyzing a recently published human chromosome 21 dataset. Analysis o f simulated datasets demonstrates that MEIVLA is superior to previous metho ds of tetrad frequency estimation and is particularly well suited to analyz e samples where the E-0 tetrad frequency is low and sample sizes are small, conditions likely to be met in most samples from human populations. We dis cuss the implications of our analysis for determining whether an achiasmate system exists in humans to ensure the proper segregation of Eo tetrads.