SNP and haplotype mapping for genetic analysis in the rat

The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies.     

Germline rates of de novo meiotic deletions and duplications causing several genomic disorders

Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome.     

Distinct stem cells contribute to mammary gland development and maintenance

The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers.     

Great Basin summer range forage quality: do plants nutrients meet elk requirements?

Understanding the relative ability of forages to meet the needs of prime-age females, the productive component of elk ( Cervus elaphus ) populations, is necessary to decipher reasons for declines and potential for population growth. Information on forage nutrient dynamics for elk on Great Basin summer-fall ranges is lacking. Our primary objectives were to estimate nutrient levels in common elk forage species in northeastern Nevada at 3 time periods and evaluate whether nutrient levels met good requirements for lactating cow elk at time periods across summers. We compared crude protein, digestible energy, and macromineral levels in 2 forbs, 6 grasses, and 4 woody browse forage species to requirements for lactating cow elk in early summer, midsummer, and early fall 1999 and 2000. Spurred lupine ( Lupinus caudatus ) and snowbrush ceanothus ( Ceanothus velutinus ) were the most proteinaceous plants, exceeding requirements across all seasons. By midsummer, protein levels in all grasses were below elk requirements (12%). Digestible energy was the most limiting nutrient with woody browse meeting lactating cow elk requirements only in early fall (2750 kcal · kg -1 ). Sodium levels never exceeded about 10% of the required 600 μg · g -1 . The potential for maintaining a relatively high density of elk at forage-quality levels that fulfill requirements declines as summers progress on Great Basin summer ranges. Maintaining highly productive elk herds in the Great Basin requires that managers maintain plant communities with a diversity of forbs, grasses, and browse to provide for nutritional needs of lactating cows and their growing calves.     

Heme synthetase in thalassemia

Zusammenfassung Hämsynthetase (HS)-Aktivität zirkulierender Retikulozyten und Erythrozyten von Normalspendern und Patienten mit Thalassämie wurde in vitro bestimmt. HS war normal oder erhöht bei Thalassämie. Jugendliche, über das Stadium des Retikulozyten hinaus gereifte Erythrozyten enthalten wahrscheinlich noch einen signifikanten Anteil der im peripheren Blut messbaren HS-Aktivität.