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The American Journal of Medical Genetics publishes 40 issues a year on all biological and medical aspects of genetic disorders and birth defects for physicians medical geneticists and associated professionals. The Journal's primary purpose is to report original research in the following areas: Biochemical Genetics including newborn screening carrier detection and the metabolic dysplasia and malformation syndromes; Cancer Genetics and Cancer Cytogenetics including experimental and molecular approaches; Clinical Genetics including descriptions of new syndromes new causal and pathogenetic insights into known syndromes advances in genetic counseling nosology anthropometry and anthropology including dermatoglyphics; Clinical Molecular Genetics including linkage mapping and gene sequencing; Formal Genetics including quantitative population and epidemiological genetics; Molecular Cytogenetics including delineation of syndromes due to chromosomal aberration; Neuropsychiatric Genetics including reports on novel research on the genetic mechanisms underlying psychiatric and neurological disorders; Reproductive Genetics including prenatal diagnosis and the genetics of prenatal and perinatal death in humans. Reports on animal models of human genetic disorders ethical legal and social issues fetal genetic pathology and teratology Genetic Drift historical aspects of medical genetics and studies of twins and twinning are appropriate for the Special Features section of the Journal. Discontinued now American Journal of Medical Genetics Part A, B and C.
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Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in the critical region as the disease gene.
The urofacial (Ochoa) syndrome (UFS) is a rare autosomal recessive disorder characterized by abnormal facial expression and urinary abnormalities. Previously, we mapped the gene to a genomic interval of approximately 1 cM on chromosome region 10q23-24, using families from Columbia. Here we demonstrate genetic homogeneity of the syndrome through homozygosity mapping in American patients with Irish heritage. We established a physical map and identified novel polymorphic markers in the UFS critical region. Haplotype analysis using the new markers mapped the UFS gene within one YAC clone of 1,410 kb. We also determined the precise location of the gene encoding for glutamate oxaloacetate transaminase (GOT1) within the new UFS critical region and determined its genomic structure. However, mutation analysis excluded GOT1 as a candidate for the UFS gene.
被引量：6 发表：1999
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An efficient, robust and unified method for mapping complex traits (III): combined linkage/linkage-disequilibrium analysis.
Extending the method for linkage analysis [Zhao et al., 1998a: Am. J. Med. Genet. 77:366-383; 1998b: Am. J. Med. Genet. 79:49-61], this article describes a method for the linkage-disequilibrium analysis, and for combining linkage and linkage-disequilibrium analyses. As highly dense markers are increasingly used in genome scans, one or more markers are not only linked with the disease genes if they exist, but also likely in linkage-disequilibrium with those putative genes. Hence, linkage-disequilibrium analysis potentially offers additional information about positions of putative disease genes. Combining both linkage and linkage-disequilibrium signals, this approach is able to improve positional signals. As before, the proposed method is a model-based approach, but semiparametric via the estimating equation technique. Under the assumptions of penetrance and allele frequency, this method efficiently estimates recombination fractions for linkage analysis and odds ratios for linkage-disequilibrium analysis. As described in two previous papers, this method is relatively more robust than the lod score methods, since it requires weaker assumption than conditional independence. While the estimated recombination fractions are used for inference as part of linkage analysis, the estimated odds ratios are used for linkage-disequilibrium inference and combined linkage, and linkage-disequilibrium parameters can be used to test combined linkage/linkage-disequilibrium analysis. This approach has been implemented, named gSCAN, and its compiled version is available for trial on request via the web site (http:/lynx.fhcrc.org/qge). We applied this new approach to affected sib-pair data collected for the genome scan to localize type 1 diabetes genes. Under an assumed autosomal dominant gene model, the linkage analysis confirms an earlier suggestion of one major gene around D6S281. Interestingly, the linkage-disequilibrium analysis suggests several additional signals around D6S250, GATA30, D6S311, D6S441, D6S442, D6S415, D6S411, D6S305, and a290xh9. The linkage analysis, on the other hand, suggests a signal around D6S281, while providing supporting evidence for several other marker loci. However, the combined analysis did not provide strong support for any of the findings, implying that linkage and linkage-disequilibrium findings are not consistent.
被引量：1 发表：1999
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Infantile spasms in two children with Williams syndrome.
We describe two children with Williams syndrome and infantile spasms. The diagnosis of Williams syndrome was confirmed by documentation of a deletion of the elastin gene/Williams syndrome region at 7q11.23. The diagnosis of infantile spasms was confirmed through the presence of interictal hypsarrhythmia. This represents one of the first reports of infantile spasms in the Williams syndrome.
被引量：3 发表：1997
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Inferring mode of inheritance by comparison of lod scores.
One usually must assume a mode of inheritance when using lod scores for linkage analysis. In this study, we asked the question, "If one assumed mode of inheritance in a linkage analysis gives a higher lod score than another, does that indicate that the mode of inheritance that led to the higher lod score is more 'correct' than the other?" We simulated data under a variety of penetrances, assuming either dominant or recessive inheritance. We then analyzed those simulated data under the correct mode of inheritance, assuming a range of penetrance values, and under the incorrect model, also assuming a range of penetrance values. We found that, if there was enough information for a maximum lod score of at least 3.0, assuming the correct penetrance value or mode of inheritance in the analysis led to a higher lod score than assuming the incorrect penetrance or the incorrect mode of inheritance. These results cannot yet be generalized outside of the specific modes of inheritance and penetrance combinations that we have modeled. Also, penetrance was modeled as "random." The effect of "reduced penetrance" caused by other genetic factors has not yet been tested. We also tested the effect of non-standard ascertainment on drawing conclusions about mode of inheritance from linkage data. Even when families were ascertained only if the family was multiplex (i.e., more than one affected sib), assuming the correct mode of inheritance gave a higher lod score than assuming the incorrect mode of inheritance. This method has the promise of both simplifying and expanding the application of linkage analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
被引量：35 发表：1989
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Effect of heterogeneity and assumed mode of inheritance on lod scores.
Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)
被引量：14 发表：1992
