Bayesian Assessment of Genetic Risk in Families with a Balanced Translocation

Abstract

An important problem from the field of genetics involves the calculation of a personalized risk estimate on behalf of a heterozygous carrier of a balanced translocation. Though phenotypically normal, the carrier may be at increased risk of having a child who is mentally and physically abnormal due to an unbalanced translocation of chromosomal segments. An accurate estimate of the probability of this event is understandably desirable. Unfortunately, translocations are almost always family-specific so there is very little data that are perfectly relevant and one has to rely heavily on general risk figures derived from studies of families with similar translocations. This makes the problem particularly well suited to Bayesian analysis, which coherently combines family-specific data and a priori knowledge. However, much of the genetics counseling literature recommends an either/or approach: if the family is large enough, use family data; else, use pooled population data. In this article, we describe how uncertainty can be significantly reduced by incorporating all available information in the context of deriving a risk estimate for a hypothetical familial translocation.

Autosomal reciprocal translocations: prenatal selection, segregation and assessment of empirical risks for reciprocal translocation carriers of having a liveborn child with chromosome imbalance

“…Íî, ê ñîaeàëåíèþ, ïîäàâëÿþùåå áîëüøèíñòâî òðàíñëîêàöèé ÿâëÿþòñÿ óíèêàëüíûìè â ñèëó áåñêîíå÷íîãî ðàçíîîáðàçèÿ òî÷åê ðàçðûâîâ íà õðîìîñîìàõ, â ñâÿçè ñ ÷åì òàêèå äàííûå ïîëó-÷èòü êðàéíå çàòðóäíèòåëüíî. Ïîýòîìó ñòðàòåãèÿ îöåíêè ðèñêà ïðè ñåìåéíîì íîñèòåëüñòâå õðîìîñîìíûõ ïåðåñòðîåê, â òîì ÷èñëå ÀÐÒ, òàêîâà, ÷òî, åñëè ñåìüÿ äîñòà-òî÷íî áîëüøàÿ ïî ÷èñëåííîñòè è èìååòñÿ òî÷íàÿ èíôîðìàöèÿ î ðåïðîäóêòèâíîì àíàìíåçå, ôåíîòèïå è êàðèîòèïå êàê ìîaeíî áîëüøåãî êîëè÷åñòâà ÷ëåíîâ ñåìüè, òî îïðåäåëÿþò ýìïèðè÷åñêèå öèôðû ðèñêà, â ïðîòèâíîì ñëó÷àå èñïîëüçóþò îáîáùåííûå ïîïóëÿöèîííûå äàííûå [5].…”

“It becomes your whole life”—Exploring experiences of reciprocal translocation carriers and their partners

“…Some couples want to know the chance of conceiving a pregnancy affected with an unbalanced translocation regardless of the chance of that pregnancy advancing towards full term. Given translocations are unique to the family or individual within which they occur, a Bayesian approach is recommended for an accurate reproductive risk assessment (VanDerwerken, 2015). Discussing the complexities in estimating reproductive risk is central in genetic counseling to help carriers make informed choices regarding reproductive options and genetic testing.…”