Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.     

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.     

Summer habitat use and selection by female Sage Grouse ( Centrocercus urophasianus ) in Oregon

Cover types and vegetative characteristics (e.g., grasses, forbs, shrubs) used by female Sage Grouse ( Centrocercus urophasianus ) during summer were compared with available habitat on two study areas in southeastern Oregon. Broodless hens, which constituted 114 of the 125 (91%) radio-marked hens studied, selected big ( Artemisia tridentata ) subspp.) and low sagebrush ( A. arbuscular ) cover types at both study areas. At Hart Mountain, broodless hens did not select specific vegetative characteristics within cover types. However, at Jackass Creek, forb cover was greater ( P = .004) at broodless hen sites than at random locations. Differences in habitat use by broodless hens between study areas were associated with differences in forb availability. Broodless hens used a greater diversity of cover types than hens with broods. Broodless hens gathered in flocks and remained separate from but near hens with broods during early summer. By early July broodless hens moved to meadows while hens with broods remained in upland habitats.     

Fall diet of blue grouse in Oregon

The early fall diet of Oregon blue grouse ( Dendragapus obscurus pallidus ) from Wallowa County, Oregon, was determined from 145 crops obtained during 1981 and 1982. Of more than 50 plant and animal foods in the diet, short-horned grasshoppers ( Acrididae ), prickly lettuce ( Lactuca serriola ), yellow salsify ( Tragopogon dubius ), wild buck-wheat ( Eriogonum spp.), and snowberry ( Symphoricarpos albus ) occurred in 30% or more of the crops and collectively amounted to 68% of the diet by weight. Seven of the 12 most common foods were consumed differentially by the four sex and age classes of birds. Results indicated that blue grouse foraged in forest and grassland habitats.     

Diversification within the Mexican vole ( Microtus mexicanus ) and the role of post-Pleistocene climate change

Normal 0 false false false MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} To examine the partitioning of genetic variation within the Mexican vole ( Microtus mexicanus ), we analyzed variation within the cytochrome b (cyt b, ca. 953 bp) from 44 samples of the Mexican vole from the mountains of the southwestern United States and Mexico. Phylogeographic analyses demonstrated strong support for a western clade and an eastern clade, corresponding to the Sierra Madre Occidental and mountains of the southwestern United States (western clade) and the Sierra Madre Oriental and the Sierra Madre del Sur (eastern clade). Levels of genetic distinctiveness among vole populations in Mexico and the southwestern United States support recognition of the Mogollon vole ( Microtus mogollonensis ). Estimates of lineage divergence suggested an older divergence for populations in Mexico and a more recent divergence for the presumptive M. mogollonensis. Ecological analyses demonstrated a distinct climate niche between vole lineages in the Southwest and Mexico, which indicated the possible role of environmental variation in diversification of the Mexican vole. A similar pattern of climatic separation was also demonstrated between clades of the codistributed taxa Sigmodon hispidus, Neotoma mexicana, and Peromyscus truei, suggesting a broader role for climatic variation in the origin and maintenance of the region’s biodiversity. Para examinar la distribución de la variación genética en el metorito mexicano, analizamos la variación en el citocromo b (cyt b, c. 953 pb ) en 44 muestras del metorito mexicano de las montañas de México y del suroeste de Estados Unidos. Los análisis filogeográficos demostraron fuerte apoyo para un clado occidental y un clado oriental, correspondientes a la Sierra Madre Occidental y las montañas del suroeste de Estados Unidos (oeste) y la Sierra Madre Oriental y la Sierra Madre del Sur (este). Los niveles de diferencia genética entre las poblaciones de metoritos en México y las del sur de Estados Unidos apoyan el reconocimiento del metorito Mogollon ( Microtus mogollonensis ) como especie. Las estimaciones de divergencia entre linajes indican una divergencia más remota para las poblaciones en México y una más reciente para el presunto M. mogollonensis. Los análisis ecológicos demuestran nichos climáticos distintos entre los linajes de metorito en el suroeste de Estados Unidos y en México, lo cual indica el posible papel de la variación ambiental en la diversificación del metorito mexicano. Un patrón similar de separación climática fue también demostrado entre clados de los taxones codistribuidos: Sigmodon hispidus, Neotoma mexicana y Peromysus truei, sugiriendo que la variación climática tiene un mayor papel en el origen y el mantenimiento de la biodiversidad de la región.     

Involvement of p34cdc2 in establishing the dependency of S phase on mitosis

Mutants of cdc2+ can disrupt the dependency of S phase on completion of the previous mitosis. By changing the state of p34cdc2 it is possible to reprogramme a cell from entering mitosis to undergoing S phase. This leads to the proposal that the cell cycle can be considered a p34cdc2 cycle, and has implications for the evolution of life cycles.     

Structure of a genomic clone encoding biologically active human relaxin

Relaxin is a peptide hormone synthesized in the corpora lutea of ovaries during pregnancy and is released into the blood stream prior to parturition. Its major biological effect is to remodel the mammalian reproductive tract to facilitate the birth process. Determination of the structure of human relaxin is thus a first step in opening up the possibility of clinical intervention in cases of difficult labour. However, the limited availability of human ovaries during pregnancy has prevented both direct amino acid sequence determination and isolation of cDNA clones obtained from relaxin producing tissue. Our approach has therefore been to screen directly for a human relaxin gene using an homologous porcine relaxin cDNA probe. We report here the successful identification of a genomic clone from which the structure of the entire coding region of a human preprorelaxin gene has been determined. Synthesis of biologically active relaxin has shown that the novel gene structure described herein codes for an authentic human relaxin. We believe this is the first successful synthesis of a biologically active hormone whose structure was predicted solely from the structure of a genomic clone.