In recent years, cytogenetic studies of spontaneous abortion products have disclosed a relatively high frequency of aneuploid embryos. These karyotypic anomalies chiefly stem from meiotic errors affecting the distribution of the chromosomes in one of the two gametes. This information not only implies the remarkable frequency of gonocyte aneuploidy but also reveals the prevalence of certain types of errors. It follows that gametal haploidy is often altered by the loss (nullisomy) or the addition (disomy) of certain members, in particular the X, the Y , and chromosomes 15, 16, 2 1, and 22.could result from the random union of a disomic gamete with a gamete nullisomic for the homologue. To this hypothetical phenomenon -which is, however, statistically likely and foreseeable -we have ascribed the name of uniparental disomy, owing t o the fact that both members of such a pair arise from only one parent. Furthermore, such a mechanism implies the probability of introducing into the genome pairs of chromosomes with whole sequences of identical alleles, a consequence which we describe by the neologism of isodisomy. Such homozygosity for a series of colinear alleles implies, from the genetic standpoint, risks and advantages akin t o those of parental consanguinity.An analogous mechanism could also modulate and modify the consequences of trisomies in which entire segments of two of the three implicated chromosomes, including the supernumerary one, could as well be isoallelic (isodisomic trisomy or di-isotrisomy ). This article briefly states some other predictions stemming from the concept of uniparental disomy, whose confirmation should serve as a test of the proposed hypothesis. Therefore, it is t o be expected that, in some exceptional zygotes, euploidy

Uniparental disomy (UPD) in humans is caused primarily by meiotic nondisjunction events, followed by trisomy or monosomy 'rescue'. The majority of cases appear to be associated with advanced maternal age, and may be initially detected as mosaic trisomies during routine prenatal diagnosis by chorionic villus sampling or amniocentesis. In addition, structural abnormalities including Robertsonian translocations, reciprocal translocations and supernumerary marker chromosomes appear to be associated with an increased risk of UPD. Predicting the phenotypic effects of UPD is complex, as three independent factors are involved: (i) effects of trisomy on the placenta or the fetus; (ii) autosomal recessive disease due to reduction to homozygosity; and (iii) imprinted gene effects for some chromosomes. To date, UPD in humans has been reported for 25 of the 47 possible uniparental types. Imprinting effects have been established with certainty for four human chromosomes that have homology to mouse chromosomes which have been shown to have significant phenotypic effects in uniparental animals. A normal phenotype has been reported for 14 other UPD types. Thus, collection of data on UPD cases in humans is providing an imprinting map analogous to the experimentally derived imprinting map in mouse. This human imprinting map has important clinical implications, particularly in the area of prenatal diagnosis.

Approximately 1.1 billion people currently live in countries where consanguineous marriages are customary, and among them one in every three marriages is between cousins. Opinions diverge between those warning of the possible health risks to offspring and others who highlight the social benefits of consanguineous marriages. A consanguinity study group of international experts and counselors met at the Geneva International ConsanguinityWorkshop from 3 rd to 7 th May 2010 to discuss the known and presumptive risks and benefits of close kin marriages, and to identify important future areas for research on consanguinity.The group highlighted the importance of evidence-based counselling recommendations for consanguineous marriages, and of undertaking both genomic and social research in defining the various influences and outcomes of consanguinity. Technological advances infor rapid high-throughput genome sequencing (HTS), and for the identification of copy number variants by comparative genomic hybridization (aCGH) offer a significantn unprecedented opportunity to identify genotype-phenotype correlations focusing on autozygosity, the hallmark of consanguinity. The ongoing strong preferential culture of close kin marriages in many societies, and among migrant communities in Western countries, merits an equivalently detailed assessment of the social and genetic benefits of consanguinity in future studies.

No abstract