Deletions and other null alleles for genetic markers can be detected as a special case of non-Mendelian inheritance, ie when a parent and a child appear to be homozygous for different alleles. The probability to detect a deletion for a fixed overall number of investigated individuals was calculated for biallelic and multiallelic markers with varying allele frequencies. To determine the effect of increasing the number of parents and grandparents, the probability for this event was derived for a parent and one child, a trio, a trio with one grandparent and a trio with two grandparents. The results for biallelic markers show that for a fixed total number of individuals, a sample of trios with two grandparents is always more efficient than the other family types, despite a lower total number of founder chromosomes in the sample. For multiallelic markers the outcome varies. The effect of adding additional children to a nuclear family was also investigated. For nuclear families, the optimal number of children is two or three, depending on the allele frequencies. It is shown that adding children is more efficient than adding grandparents. European Journal of Human Genetics (2008Genetics ( ) 16, 1225Genetics ( -1234 doi:10.1038/ejhg.2008 published online 16 April 2008 Keywords: deletion; null allele; pedigree; genetic marker
IntroductionDeletions are one of the many types of mutations that can affect a genome. The observed size of a deletion range from a single base pair up to an entire arm of a chromosome (see Lewis 1 ). In recent years, there has been an increasing interest in investigating structural variants, including deletions. 2 One reason is because deletions may be the cause of some diseases. One such case is the occurrence of somatic deletions involved in cancer, which can be detected through 'loss of heterozygosity' in the tumour when compared to other tissues. 3 Another situation where deletions may be observed is when they occur as de novo deletions. These are notable when they subsequently cause disease in the offspring of the person within whom the deletion occurred in the germline. 4 Finally, deletions causing disease may be inherited. Such deletions may act as directly causing in one end of the spectrum, but may also act as risk alleles in complex diseases. 5,6 However, just as in the case with other types of mutations deletions may have no phenotypic effect. 7,8 Alternatively, the effect is so weak that it is effectively undetectable. Such mutations may then appear as polymorphisms within populations. The presence of deletion polymorphisms in the human genome have recently been investigated in a number of large-scale projects. 5,9 -12 These investigations demonstrate that a large number of deletion polymorphisms occur in humans. They also show that, although with few exceptions the deletion constitutes the rare allele, the frequency of the deletion may be relatively high. The presence and frequency of deletion polymorphisms is of interest for a number of reasons. In certain eukaryotic lineages such...