Evidence from studies in rodents suggests that mate selection is influenced by major-histocompatibility-complex haplotypes, with preferences for dissimilar partners. This study was initiated to determine whether avoidance of a mate with the same HLA haplotype as one's own might be occurring in the Hutterites, a North American reproductive isolate of European ancestry, notable for their large sibships, communal lifestyle, and limited number of five-locus HLA haplotypes (HLA-A, -B, -C, -DR, and -DQ). HLA haplotypes were known for 411 Hutterite couples. The number of couples expected to match for a haplotype was calculated in two ways: first, from population genotype frequencies, with account being taken of the nonrandom mating pattern with respect to colony lineages, and, second, from computer simulations using conservative founder assumptions and the exact genealogy of the 411 couples. We observed fewer matches for HLA haplotypes between spouses than expected (first method, P = .005; second method, P = .020-.067). Among couples who did match for a haplotype, the matched haplotype was inherited from the mother in 29 cases and from the father in 50 cases (P = .018). These results are consistent with the conclusion that Hutterite mate choice is influenced by HLA haplotypes, with an avoidance of spouses with haplotypes that are the same as one's own.

The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.

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In spite of the centrality of informed consent in clinical genetics and genomics, new recommendations from the American College of Medical Genetics and Genomics (ACMG) call for laboratories and clinicians to test for and report specific genetic incidental findings, even when the patient does not consent to the testing or disclosure and even when the patient is a child.

The role that maternal and fetal human leukocyte antigen (HLA) genes play in pregnancy is unknown, but it has been suggested that fetuses whose HLA alleles do not differ from maternal alleles (i.e. histocompatible fetuses) are more likely to be aborted than fetuses with HLA alleles that differ from maternal alleles (i.e. histoincompatible fetuses). To elucidate the role of HLA compatibility in pregnancy, we tested the hypothesis that couples who match for HLA alleles or haplotypes would have reduced fertility because only these couples could produce histocompatible fetuses. We conducted a 10 year prospective study of HLA matching and pregnancy outcome in 111 Hutterite couples, providing information on 251 pregnancies. A logistic regression analysis was performed to determine the effects of HLA matching at HLA regions and loci on pregnancy outcome (fetal loss versus delivery). Significantly increased fetal loss rates were observed among couples matching for the entire 16-locus haplotype (P = 0.002). Among the individual loci, loss rates were increased among couples matching for HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P = 0.043). We interpret these results as evidence that matching for the entire 16-locus haplotype and/or alleles at an HLA-B-linked locus confers significant risk for fetal loss.

Flow cytometry can be used to obtain high-resolution estimates of nuclear DNA content (8,12,27). Much of the work in this area has been confined to clinical studies in the human, but the technology has been extended to organisms such as pocket gophers (241, triploid trout ( 2 3 , side-necked turtles (61, sex-reversed horses (16), and oysters (1).In these and similar studies, the DNA content of target cells is quantified relative to a standard DNA content in cells from a reference species (13,14,28). Standards may be used as internal references, when target cells and reference cells are mixed together and assayed simultaneously, or as external references, when target cells and cells from the reference species are analyzed independently. When external references are used, the flow cytometer must be checked for equilibration between analyses.The standard can be used for several calculations. The standard can be assigned a known DNA mass, against which picogram quantities of nuclear DNA from target cells can be estimated directly (15). Alternatively, a standard could be used as an internal reference in the analysis of individual samples, following which the reference is cancelled during estimation of a DNA Index. An internal reference would also be cancelled during the calculation of picogram quantities of nuclear DNA relative to a separate standard that has a known DNA mass (and a known relationship to the internal reference). These last two calculations do not require knowledge of the precise DNA mass of the internal reference.Because the use of reference standards provides a relative measure of DNA content, it is crucial that the reference cells and the target cells have a similar DNA content to minimize possible zero shift error (28) and, in the case of a n internal reference, that the values for the reference and target cells do not overlap.In order to gather information relating to the selection of reference standards for use in flow cytometry, we have surveyed a wide spectrum of taxa representing each of the major vertebrate classes. Here we present the results of our survey in 45 species. These species were selected because of their broad distribution and general accessibility, and because they provide an array of fluorescence peaks spanning the range of DNA masses that might be encountered in comparative studies. ~~~

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Background: Analysis of fetal DNA from maternal plasma by PCR offers great potential for noninvasive prenatal genetic diagnosis. To further evaluate this potential, we developed and validated a standard protocol to determine whether fetal DNA sequences could be reproducibly amplified and measured across multiple laboratories in a common set of specimens. Methods: Each of five participating centers in a National Institute of Child Health and Human Development consortium collected 20 mL of peripheral blood from 20 pregnant women between 10 and 20 weeks of gestation. The plasma fraction was separated according to a common protocol, divided, and frozen in five aliquots. One aliquot was shipped to each participating laboratory, where DNA was extracted according to a standard protocol. All plasma samples (n ‫؍‬ 100) were then analyzed blindly for the presence and quantity of total DNA (GAPDH) and male fetal DNA (SRY) by real-time PCR. Genomic DNA was isolated from female and male cells at one center, quantified, and shipped to