ABSTRACT
Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome scan using a set of 364 families with a panel of 396 microsatellite markers was conducted. Nonparametric linkage analyses were conducted for asthma and three asthma-related phenotypes: bronchial hyper-reactivity (BHR), strict definition of asthma and atopic asthma. Nine chromosomal regions with LOD scores greater than 1.5 were identified (chromosomes 1q, 2p, 3q, 4p, 4q, 6q, 12q, 20p and 21). Linkage refinement analysis was performed for three BHR loci by genotyping single nucleotide polymorphisms at an average marker density of 1 cM. The LOD scores increased to 3.07 at chromosome 4p and 4.58 at chromosome 2p, while the chromosome 6p locus did not refine. The LOD score at the chromosome 2p locus is highly significant on a genome-wide basis. The refined locus covers a region with a physical size of 12.2 Mb. Taken together, these results provide evidence for a major asthma susceptibility locus on chromosome 2p.
Subject(s)
Asthma/genetics , Chromosomes, Human, Pair 2 , Genetic Linkage , Genome , Adolescent , Adult , Child , Chromosome Mapping , Family Health , Female , Genetic Predisposition to Disease , Humans , Lod Score , Male , Microsatellite Repeats , Middle Aged , Models, Genetic , Models, Statistical , Phenotype , Polymorphism, Single Nucleotide , Quality ControlABSTRACT
Twenty-nine multiparous cows of each of the Jersey and Friesian breeds, all kappa-casein AB phenotype, were grazed together and managed identically. On three occasions during 10 d in spring (early lactation), milk was collected from all cows at four consecutive milkings and bulked according to breed. On a separate occasion, milk samples were also collected from each cow at consecutive a.m. and p.m. milkings to form one daily sample per cow. The bulked milks (800-1000 l per breed on each occasion) were standardized to a protein:fat (P:F) ratio of 0.80, and 350 l from each breed was made into Cheddar cheese. The solids content of the remaining Friesian milk was then increased by ultrafiltration to a solids concentration equal to that of the Jersey milk. This solids-standardized Friesian milk and a replicate batch of P:F standardized Jersey milk were made into two further batches of Cheddar cheese in 350-l vats. Compared with Friesian milk, Jersey milk had higher concentrations of most milk components measured, including protein, casein and fat. There were few difference in milk protein composition between breeds, but there were differences in fat composition. Friesian milk fat had more conjugated linoleic acid (CLA) than Jersey milk fat. Jersey milk coagulated faster and formed firmer curd than Friesian milk. Concentrations of some milk components were correlated with coagulation parameters, but relationships did not allow prediction of cheesemaking potential. Jersey milk yielded 10% more cheese per kg than Friesian milk using P:F standardized milk, but for milks with the same solids concentration there were no differences in cheese yield. No differences in cheese composition between breeds were detected. Differences in cheesemaking properties of milk from Jerseys and Friesians were entirely related to the concentrations of solids in the original milk.
Subject(s)
Cattle , Cheese , Milk/chemistry , Animals , Caseins/analysis , Cheese/analysis , Chemical Phenomena , Chemistry, Physical , Female , Lactation , Linoleic Acids, Conjugated/analysis , Lipids/analysis , Milk Proteins/analysis , Phenotype , Seasons , Species SpecificityABSTRACT
In the course of our search for the gene responsible for X-linked cone-rod dystrophy (COD1), we constructed a physical map and contig (encompassing the region between DXS556 and DXS228), and identified sequences showing homologies to the expressed sequence tags (ESTs) that matched CRSP2 (EXLM1) transcript. We confirmed the expression of the CRSP2 gene in the retina and refined its exact genomic location between DXS1368 and DXS993. We demonstrated that the entire transcript is encoded within 31 exons. Primers were designed for mutation analysis of the exons by direct sequencing of PCR products from genomic DNA, and revealed no mutations in COD1 families. We subsequently excluded CRSP2 as a candidate for COD1 by demonstrating the causative mutations in the RPGR. However, due to its expression in different tissues and its contribution to transcriptional regulation, CRSP2 may be a candidate for other diseases that map to this region of the X chromosome.
