Appendix A: Minimal genetic screening for gamete donors

Abstract

I.The DonorA.Should not have any major mendelian disorder. Mendelian disorders fall into the following categories:1.Autosomal dominant or X-linked disorders in which age of onset extends beyond the age of the donor, such as Huntington disease.2.Autosomal recessive inheritance (homozygous). Donors who are heterozygous need not necessarily be excluded if recipients are not also heterozygous.B.Should not have (or have had) any major malformation of complex cause (multifactorial/polygenic), such as spina bifida or heart malformation. A major malformation is defined as one that carries serious functional or cosmetic handicap. However, the definition of “major” is a matter of judgment.C.Should not have any significant familial disease with a major genetic component. This applies especially to first-degree relatives (parents, siblings, or offspring).D.Should not carry a known karyotypic abnormality that may result in chromosomally unbalanced gametes. Among healthy young adults, the chance of having a chromosomal rearrangement that could be transmitted in unbalanced form to offspring is small. For this reason, routine karyotypic testing of all donors is optional.E.A member of a high-risk group (see Table A1) should be tested routinely to determine heterozygosity for certain conditions. The list of tests may change as new tests for other disorders are developed. Heterozygosity need not necessarily exclude a donor, but certain donors may be inappropriate in a given case.F.New screening guidelines for cystic fibrosis in the general population have been developed recently by the American College of Obstetricians and Gynecologists and other organizations, and are applicable for gamete donors. Functionally, all gamete donors should be evaluated by the current tests recommended at the time of the donation.G.Donors should be generally healthy and young. Males 40 years and older are at increased risk for new mutations. Women 35 years and older are at increased risk for producing offspring with aneuploidy.II.The donor's first-degree relatives (parents, siblings, or offspring) should be free of:A.Mendelian disorders as described in Section I.A.B.Major malformations as described in Section I.B.C.A chromosomal abnormality, unless the donor has a normal karyotype.D.If family history reveals a disorder for which definitive testing is available, and it is important to consider that candidate further as a donor, then it is appropriate to test for that specific disorder. Results will determine appropriateness of donor.