Network-based informatics support of research collaborations in the Human Genome Project and the Human Brain Project
PubMed, 1995
Sophisticated network-based informatics support will increasingly be required for collaborating b... more Sophisticated network-based informatics support will increasingly be required for collaborating biomedical laboratories located in different geographic locations, both to accommodate the massive amount of data being generated in certain fields, and to allow different types of data produced at different laboratories to be analyzed in an integrated fashion. The paper describes the experience of the Yale Center for Medical Informatics in providing informatics support for collaborative projects in gene mapping (as part of the national Human Genome Project) and neuroscience (as part of the national Human Brain Project). The paper describes the informatics needs of the two projects and the solutions being developed, describes certain lessons learned, and discusses certain broader issues that arise.
Session Introduction
The CEPH consortium linkage map of human chromosome 16
HAL (Le Centre pour la Communication Scientifique Directe), 1995
International audienceA Centre d'Etude du Polymorphisme Humain (CEPH) consortium map of human... more International audienceA Centre d'Etude du Polymorphisme Humain (CEPH) consortium map of human chromosome 16 has been constructed. The map contains 158 loci defined by 191 different probe/restriction enzyme combinations or primer pairs. The marker genotypes, contributed by 9 collaborating laboratories, originated from the CEPH families DNA. A total of 60 loci, with an average heterozygosity of 68%, have been placed on the framework genetic map. The genetic map contains 7 genes. The length of the sex-averaged map is 165 cM, with a mean genetic distance between loci of 2.8 cM; the median distance between markers is 2.0 cM. The male map length is 136 cM, and the female map length is 197 cM. The map covers virtually the entire chromosome, from D16S85, within 170 to 430 kb of the 16p telomere, to D16S303 at 16qter. The markers included in the linkage map have been physically mapped on a partial human chromosome 16 somatic cell hybrid panel, thus anchoring the genetic map to the cytogenetic-based physical map
Primate Research Supplement International Primatological Society, 2010
By increasing the number of genes, gene duplication allows gain of new functions and properties, ... more By increasing the number of genes, gene duplication allows gain of new functions and properties, and is one of the most important mechanisms for genome evolution. The alcohol dehydrogenase (ADH) gene family exists widely in the genomes of many organisms, and provides a fine model for evolution of gene families. The seven human ADH genes are classified into five classes based on nucleotide/amino acid sequence similarity. Mice have six ADH genes in the same order as humans. One of the most interesting differences between humans and mice is that mice have only one Class I gene. The three Class I genes (ADH1A, ADH1B, ADH1C) in humans show very high nucleotide similarity both in exons (> 90%) and introns (> 70%), suggesting duplication events occurred probably after primates diverged from rodents. We have proposed a hypothesis that the primates' frugivorous behavior has maintained the duplicated genes because of the necessity of digesting ethanol generated by fermentation of fruit sugar. To test the hypothesis, we are screening the BAC clone libraries of 11 primates, and sequencing the ADH cluster clones in order to obtain nucleotide sequence information for the whole region of the gene cluster in the primates. Initial analyses of the three Class I genes suggest that the Class I genes have evolved without concerted evolution. Here we present the progress of the sequencing on the ADH gene cluster evolution in primate lineage.
Testing of Evolutionary Independence in Simulated Phylogenetic Trees
Systematic zoology, Dec 1, 1978
... Genetica, Universitd di Pavia 27100 Pavia, Italy), A. Piazza (Istituto di Genetica Medica, Un... more ... Genetica, Universitd di Pavia 27100 Pavia, Italy), A. Piazza (Istituto di Genetica Medica, Universitd di Torino, 10100 Torino, Italy), and KK Kidd (Department of ... At this time the two variate techniques, and tests of hypothe-daughter populations have the same val-ses can be set up ...
An analysis of the genetics of schizophrenia
Social biology, Sep 1, 1973
Abstract Data on the inheritance of schizophrenia indicate that both genetics and environment con... more Abstract Data on the inheritance of schizophrenia indicate that both genetics and environment contribute importantly to the manifestation of the disease. However, heterogeneity of the data makes an accurate analysis very difficult. In this paper, a crude analysis of a threshold model, using a polygenic or a single gene hypothesis, shows that both are in approximate agreement with the data. Though argument about genetic models seems futile when virtually any model can account for the data, the single gene hypothesis is unavoidably more attractive at this stage. If a single gene is involved, the allele predisposing toward schizophrenia should be considered as essentially, though not entirely, recessive; all genotypes would be strongly affected by unknown environmental factors; and even some genetically normal individuals would manifest the disorder.
Abstracts of workshop presentations pp. 1075-1091
Cytogenetic and Genome Research, 1989
Low linkage disequilibrium at the dopamine D4 receptor (DRD4) gene in the telomeric region of chromosome 11
The search for the gene that causes the multiple endocrine neoplasia type 2A (MEN 2A) syndrome is... more The search for the gene that causes the multiple endocrine neoplasia type 2A (MEN 2A) syndrome is entering a new phase. Genetic linkage studies have localized the gene to the pericentromeric region of chromosome 10. The statistical portion of mapping the gene for MEN 2A is nearly complete and now classical molecular biological/gene mapping techniques will be employed. We have used fluorescence in situ hybridization to estimate the size of the MEN2A region to be about 2 to 5 mb, using some liberal assumptions; at worst the region should contain no more than about 10 mb of non-alphoid DNA. Our mapping panels (meiotic recombinant and radiation reduced hybrid) give consistent orders of markers in this small region. We describe our initial attempts to clone the region using yeast artificial chromosomes.
Probable linkage between the human galactose-1-P uridyl transferase locus and 9qh
PubMed, Mar 1, 1980
Evaluation of a family in which electrophoretic variants of the eznyme galactose-1-phosphate urid... more Evaluation of a family in which electrophoretic variants of the eznyme galactose-1-phosphate uridyl transferase (GALT) and 9qh variants occur demonstrates close linkage between these two traits: lod score of 3.67 at theta = 0. Taken with information indicating GALT is on the short arm of chromosome 9, these linkage data suggest that this locus is close to the centromere on the short arm of chromosome 9.
The pseudoautosomal boundary is defined by an Alu repeat element on the Y chromosome. The Alu ele... more The pseudoautosomal boundary is defined by an Alu repeat element on the Y chromosome. The Alu element is found on all Y chromosomes and on no X chromosomes, establishing it as part of Y-specific sequences. Distal to the Alu element, sequences from the X and Y are strictly homologous, suggesting that the boundary is formed by an abrupt break in sequence homology. Further investigation of the function of the boundary has been undertaken by examining the population structure of an MspI restriction-site polymorphism (XY274), which is located 274 bp distal to the Alu insertion site. Southern blot and polymerase chain reaction analysis demonstrate fixation of the high allele (noncutting or AT base pair) of XY274 on the Y chromosome in most populations, while a full range of high allele frequencies is found on the X chromosomes of different populations. Two exceptions to fixation on the Y chromosome were found in African populations. The level of linkage disequilibrium suggests that the first few hundred base pairs of the pseudoautosomal region on the Y chromosome share a single common origin more recent than the origin of the species.
Apparent monomorphism of ALDH2 in seven American Indian populations
Alcohol, Mar 1, 1995
Deficiency of mitochondrial aldehyde dehydrogenase (ALDH2) has been previously reported in South ... more Deficiency of mitochondrial aldehyde dehydrogenase (ALDH2) has been previously reported in South American Indians. We therefore assayed five individuals from each of five South American Indian populations (Quechua, Karitiana, Ticuna, Surui, Guahiba), and two North American populations (Maya and Moskoke) for the presence of the Oriental ALDH2(2) variant. These samples were also surveyed for other alleles altering ALDH2 function. Allele-specific amplification assay (ASA) did not detect the ALDH2(2) allele in any of the New World populations studied. The entire coding sequence of the ALDH2 cDNA was enzymatically amplified in partially overlapping fragments. Each fragment was digested using restriction endonucleases and subfragments 148-285 b.p. in length were analyzed by the single-stranded conformation polymorphism (SSCP) technique. No variants were detected within the coding region of the ALDH2 gene in any of the seven American Indian populations. Three potentially correct explanations for these results are suggested. First, an ALDH2 polymorphism is present but undetectable by SSCP; second, none of the studied individuals were ALDH2 negative; third, the polymorphism occurs beyond the coding region of ALDH2 gene.
Micronesia began to be peopled earlier than other parts of Remote Oceania, but the origins of its... more Micronesia began to be peopled earlier than other parts of Remote Oceania, but the origins of its inhabitants remain unclear. We generated genome-wide data from 164 ancient and 112 modern individuals. Analysis reveals five migratory streams into Micronesia. Three are East Asian related, one is Polynesian, and a fifth is a Papuan source related to mainland New Guineans that is different from the New Britain–related Papuan source for southwest Pacific populations but is similarly derived from male migrants ~2500 to 2000 years ago. People of the Mariana Archipelago may derive all of their precolonial ancestry from East Asian sources, making them the only Remote Oceanians without Papuan ancestry. Female-inherited mitochondrial DNA was highly differentiated across early Remote Oceanian communities but homogeneous within, implying matrilocal practices whereby women almost never raised their children in communities different from the ones in which they grew up.
The Human Gene Mapping Library: Present Status and Future Directions
Forensic DNA typing [7]
Science, 1992
Population genetic data of 74 microhaplotypes in four major U.S. population groups
Forensic Science International: Genetics, 2020
Microhaplotypes (microhaps or MHs) are novel forensically relevant genetic markers that demand la... more Microhaplotypes (microhaps or MHs) are novel forensically relevant genetic markers that demand large and appropriate allele frequency datasets for their implementation in casework. In this study we report on the allele frequency data of 74 microhap loci (230 SNPs) included in a newly developed 74-plex assay. The panel was tested on the Ion S5 system on a total of 347 samples from four main U.S. population groups of African, European, East Asian and Southwest Hispanic descent. Overall, frequencies of individual alleles at each locus varied considerably among the different population groups. An increase in the average value of gene diversity was also observed as the number of SNPs per locus increased. Most microhap markers showed no significant deviation from Hardy-Weinberg ratios within any of the individual population samples displaying an average power of discrimination between 0.74 and 0.81 and an average probability of exclusion between 0.32 and 0.39. Moreover, the four population groups had no clear genetic affinities with the exception of U.S. European and U.S. Southwest Hispanic populations, which showed the lowest FST value. STRUCTURE and principal component analyses (PCA) analysis resulted in effective clustering of the four populations with the U.S. European and Southwest Hispanic showing some overlap. These results support the potential use of this sequence-based 74plex-microhaplotype assay for ancestry inference in addition to previously reported human identification and mixture deconvolution capabilities.
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Papers by Kenneth Kidd