How frequently are Autosomal and X-STRs multistep mutations perceived as single-step?

Short tandem repeats (STRs) incur in length mutations that involve the loss or gain of repeats. STR mutation rates are usually estimated considering the rates of observed Mendelian incompatibilities in one generation familial configurations. When considering multistep mutations, for the autosomal and X-chromosomal modes of genetic transmission, underestimations are inevitable when using this approach (MIA), due to the occurrence of mutational events deceptively perceived as involving fewer steps. The rate of this occurrence depends on the mode of genetic transmission considered, the parental origin of the mutation, the type of familial configuration considered, and the genotypic background of the progenitor(s). MIA biases were weighted and compared for the diploid and haplodiploid modes of transmission, using familial genotypic configurations (parent(s)-child duos and trios) generated resorting to Python™ and real population databases from Norway, Somalia, and Spain for 10 Aut-STRs and Argentina, Eastern Asia, and Northern Europe for 12 X-STRs. One two- or one three-step mutation was simulated in each of the 1,000,000 familial configurations. The frequency with which mutations could be interpreted as involving fewer steps, when the most parsimonious reasoning is employed, was computed. Results showed that the magnitude and type of biases depend on the type of familial data and the genetic mode of transmission considered, being higher in duos than in trios, both in autosomes and the X chromosome. Indeed, whether X- or Aut-STRs are analyzed, trios generally provide better estimates and should be favored over duos. The pooling of the two types of data is not advised. The greater the number of steps involved in the mutation, the worst the estimates obtained. In X-chromosomal analyzes, trios with a paternal mutation presented the best estimates and mother-daughter duos the worst; mother-son duos showed similar estimates to trios when a maternal mutation was considered.