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Biomedical subjects

J H Nadeau

Publications and source records attributed to J H Nadeau.

At least 19 recordsLinked to original sources
PubMed1998

Multigenic and imprinting control of ovarian granulosa cell tumorigenesis in mice.

Spontaneous juvenile ovarian granulosa cell (GC) tumors that occur in young girls are similar to GC carcinomas that develop in SWR-derived inbred mice. We analyzed female offspring from a series of matings among SWR and SJL inbred mice for chromosomal loci underlying tumor susceptibility. Intercross F2 female mice were produced by reciprocal matings of (SWR x SJL)F1 and (SJL x SWR)F1 parents. Tumorigenesis in these F2 mice as well as in SWXJ recombinant inbred and congenic strains of mice derived from SWR and SJL showed significant (P < 0.001) association with Gct1, a dominant susceptibility locus on chromosome (CHR) 4 and with Gct2 on CHR 12. Suggestive (P < 0.01) association was found with Gct3 on CHR 15. A fourth susceptibility locus, Gct4 on CHR X, was demonstrated with a strong parent-of-origin effect associated with the paternal genotype. Imprinting and complex interactions among these four loci combine to establish the probability for GC tumorigenesis in this mouse model.

Alleles↗
PubMed1998

Counting on comparative maps.

Comparative maps record the history of chromosome rearrangements that have occurred during the evolution of plants and animals. Effective use of these maps in genetic and evolutionary studies relies on quantitative analyses of the patterns of segment conservation. We review the analytical methods that have been developed for characterizing these maps and evaluate their application to existing comparative maps mainly for plants and animals.

Animals↗
PubMed1998

Genomic strategies for defining and dissecting developmental and physiological pathways.

A major challenge in genetics research is defining and dissecting the diversity of developmental and physiological pathways that lie between genes and traits. New functional genomics methods are transforming these studies by providing comprehensive and systematic approaches that complement traditional methods of formal genetics, biochemistry, and cell biology. Together, these complementary approaches will test whether reductionism can account for the complex web of interactions that lead from genetic variation to morphological, physiological, and behavioral traits in health and disease.

Animals↗
PubMed1998

Testicular teratocarcinogenesis in mice--a review.

Spontaneous testicular germ cell tumours in humans and mice are remarkable for their diverse composition. These tumours are usually composed of an extraordinary variety of cell and tissue types including muscle, skin, bone, cartilage, and neuroepithelia. Their diverse composition reflects their origin from totipotent primordial germ cells at about Day 12 of fetal development. Although much is known about the development of these tumours, remarkably little is known about the genetics of the mammalian primordial germ cell lineage or about the genes that control susceptibility to spontaneous testicular germ cell tumours in humans or mice. Conventional genetic analysis of susceptible 129/Sv mice is difficult because of the large number of susceptibility genes and their low penetrance. We are taking advantage of the Ter mutation to simplify the genetic analysis. Various evidence suggests that Ter is neither necessary nor sufficient for tumourigenesis. Instead, Ter acts as a modifier, dramatically increasing tumour incidence from approximately 1% in +/+ males, to approximately 17% in Ter/+ males and approximately 94% in Ter/Ter males. Segregation analysis suggests that Ter increases tumour incidence by requiring some, but perhaps not all, of the 129/Sv-derived susceptibility genes. With standard crosses that segregate for the Ter mutation, identification not only of Ter but also of these 129/Sv-derived susceptibility genes should be possible. In this paper, we review the genetics and development of germ cell tumours in 129/Sv mice, summarize the status of Ter mapping, and provide evidence that different genetic pathways lead to unilateral and bilateral tumours.

Animals↗
PubMed1997

Disorganization in mice and humans and its relation to sporadic birth defects.

Disorganization (Ds) is a mouse mutant best known for producing an exceptional variety of unusual developmental anomalies, such as mirror-limb duplications and hamartomatous skin papillae. So great is the range of malformations that no two affected mice are identical. Several patients with a similar variety of exceptional anomalies have been reported, raising the possibility of the existence of a human homologue of Ds. However, although these human cases represent the most striking findings seen in Ds mice, they do not represent the full range of defects. Most affected mice have only a single malformation, and most of these malformations are similar to both common (neural tube defects, orofacial clefting, gastroschisis, limb reductions) and rare (anophthalmia, duplicated rectum) human birth defects. It is therefore possible that the full spectrum of the human homologue of Ds includes not only patients with the unusual combination of anomalies but also common sporadic birth defects. We suggest that the low penetrance (approximately 0-30%) and highly variable expression of Ds make it a paradigm for understanding the genetic basis for many seemingly sporadic birth defects.

Abnormalities, Multiple↗
PubMed1997

Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain.

The 129 mouse is the most widely used strain in gene targeting experiments. However, numerous substrains exist with demonstrable physiological differences. In this study a set of simple sequence length polymorphisms (SSLPs) was used to determine the relatedness of selected 129 substrains. 129/SvJ was significantly different from the other 129 substrains and is more accurately classified as a recombinant congenic strain (129cX/Sv), being derived from 129/Sv and an unknown strain. This mixed genetic background could complicate gene targeting experiments by reducing homologous recombination efficiency when constructs and ES cells are not derived from the same 129 substrain. Additionally, discrepancies due to different genetic backgrounds may arise when comparing phenotypes of genes targeted in different 129-derived ES cell lines.

Agouti Signaling Protein↗
PubMed1997

Angiotensin II type I receptor polymorphism in African Americans lower frequency of the C1166 variant.

The C1166 variant, an A to C substitution polymorphism at the 1166 position of the angiotensin II type I (AT1) receptor, has been previously associated with hypertension in Caucasians. This study determines the frequency of the C1166 variant in an African American population. Normotensive African American (n = 99) and Caucasian (n = 100) subjects were genotyped to determine the frequency of the C1166 variant. This study establishes the frequency of the C1166 variant in African Americans (0.05 +/- 0.01) and demonstrates a significantly lower frequency in African Americans compared with Caucasians (0.05 vs. 0.25, respectively, chi 2 = 30.7, p < < 0.001, 1 df).

Adult↗
PubMed1997

Conserved segment identification.

The quantitative study of evolution based on comparative map data is dependent on the definition and identification of conserved segments remaining after interchromosomal exchanges such as reciprocal translocation. Because of experimental error and, more important, extensive local intrachromosomal rearrangement, it is difficult to reconstruct the configuration of conserved segments produced by interchromosomal exchanges. We present a formula to evaluate possible conserved segments and an algorithm which seeks the partition of the genome into segments optimal under this evaluation. Application is made to the human-mouse comparison.

Algorithms↗
PubMed1997

Synteny conservation and chromosome rearrangements during mammalian evolution.

An important problem in comparative genome analysis has been defining reliable measures of synteny conservation. The published analytical measures of synteny conservation have limitations. Nonindependence of comparisons, conserved and disrupted syntenies that are as yet unidentified, and redundant rearrangements lead to systematic errors that tend to overestimate the degree of conservation. We recently derived methods to estimate the total number of conserved syntenies within the genome, counting both those that have already been described and those that remain to be discovered. With this method, we show that approximately 65% of the conserved syntenies have already been identified for humans and mice, that rates of synteny disruption vary approximately 25-fold among mammalian lineages, and that despite strong selection against reciprocal translocations, inter-chromosome rearrangements occurred approximately fourfold more often than inversions and other intra-chromosome rearrangements, at least for lineages leading to humans and mice.

Animals↗