30 November 2009
ByAppeared in BioNews 536
In BioNews 535, we published a commentary by Wendy Kramer in which she stated that 'using a donor with reciprocal translocations is potentially even more likely to produce sick children than donors with autosomal dominant disorders. The chances for a chromosomally abnormal child are thirty out of thirty-two (Scriven, 1998)'. However, this interpretation is incorrect and potentially misleading, the author of the paper has since informed us.
Male donors carrying balanced reciprocal translocations are expected to produce a proportion of sperm with unbalanced translocations; however, in most cases their donated sperm will not result in a child with physical and developmental problems. Approximately one in four of the donor's sperm will have a normal complement for the chromosomes involved in the translocation (i.e. one copy of each chromosome), one in four will have the same balanced translocation as the donor (meaning that these sperm have the two rearranged chromosomes and therefore there is no loss or gain of genes), and one in two will have one of a number of different possible unbalanced products of the translocation (meaning that these sperm have different combinations of normal and/or rearranged chromosomes resulting in the loss or gain of genes). These chromosomally unbalanced sperm can have between zero and three copies of the different translocation segments and the genes they contain (potentially hundreds of genes for some segments). Conceptions with a normal chromosome complement or the balanced translocation are likely to result in healthy children; however, the majority of conceptions with unbalanced translocations are incompatible with life and will result in miscarriage.
It is therefore misleading to suggest that in general sperm donated by individuals carrying reciprocal translocations have a higher risk of a 'sick child' than an autosomal dominant disorder as the live birth risk of an unbalanced translocation will be unique to the individual, ranging from zero to approximately 30 per cent, and will depend on the size of the translocation and which chromosomes have been affected. While an inherited balanced translocation does not usually result in a child with physical and developmental problems, it is likely to be associated with reproductive problems and for this reason it is still vital to karyotype gamete donors for chromosome rearrangements.