deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.

Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 () Two infants had severe combined immunodeficiency with the complete absence of T and B cells (TB SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination.

Importing genetically altered animals: ensuring quality.

The reproducibility of research using laboratory animals requires reliable management of their quality, in particular of their genetics, health and environment, all of which contribute to their phenotypes. The point at which these biological materials are transferred between researchers is particularly sensitive, as it may result in a loss of integrity of the animals and/or their documentation. Here, we describe the various aspects of laboratory animal quality that should be confirmed when sharing rodent research models.

A resource of targeted mutant mouse lines for 5,061 genes.

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes, including 2,850 novel null, 2,987 novel conditional- ready, and 4,433 novel reporter alleles.

Placentation defects are highly prevalent in embryonic lethal mouse mutants.

Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes.

Deubiquitinase MYSM1 Is Essential for Normal Fetal Liver Hematopoiesis and for the Maintenance of Hematopoietic Stem Cells in Adult Bone Marrow.

MYSM1 is a chromatin-interacting deubiquitinase recently shown to be essential for hematopoietic stem cell (HSC) function and normal progression of hematopoiesis in both mice and humans. However, it remains unknown whether the loss of function in Mysm1-deficient HSCs is due to the essential role of MYSM1 in establishing the HSC pool during development or due to a continuous requirement for MYSM1 in adult HSCs. In this study we, for the first time, address these questions first, by performing a detailed analysis of hematopoiesis in the fetal livers of Mysm1-knockout mice, and second, by assessing the effects of an inducible Mysm1 ablation on adult HSC functions.

Characterization of Distinct Tombusviruses that Cause Diseases of Lettuce and Tomato in the Western United States.

A soilborne disease of lettuce, associated with necrosis and dieback, has been found with increasing frequency in California and Arizona over the last 10 years. An isometric virus, serologically related to Tomato bushy stunt virus (TBSV), was consistently isolated from lettuce plants with these disease symptoms. Back-inoculation to healthy lettuce plants and subsequent reisolation of the virus from symptomatic lettuce leaves suggested that this virus was the causal agent of this disease.

Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis.

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene.

Host Resistance to Mirafiori lettuce big-vein virus and Lettuce big-vein associated virus and Virus Sequence Diversity and Frequency in California.

Big vein is an economically damaging disease of lettuce (Lactuca sativa) caused by the Olpidium brassicae-vectored Mirafiori lettuce big-vein virus (MLBVV). Lettuce big-vein associated virus (LBVaV) is also frequently identified in symptomatic plants, but no causal relationship has been demonstrated. Although big vein is a perennial problem in the United States, the extent of MLBVV and LBVaV infection and diversity is unknown.

Weedborne Reservoirs and Seed Transmission of Verticillium dahliae in Lettuce.

The seed transmission of Verticillium dahliae was evaluated in lettuce (Lactuca sativa). Seed collected from lettuce plants infected with V. dahliae were plated with or without surface sterilization on Sorenson's modified NP10 medium.

Genetic analysis and mapping of resistance to lettuce dieback: a soilborne disease caused by tombusviruses.

A diverse collection of modern, heirloom and specialty cultivars, plant introduction (PI) accessions, and breeding lines of lettuce were screened for susceptibility to lettuce dieback, which is a disease caused by soilborne viruses of the family Tombusviridae. Susceptibility was evaluated by visual symptom assessment in fields that had been previously shown to be infested with Lettuce necrotic stunt virus. Of the 241 genotypes tested in multiple field experiments, 76 remained symptom-free in infested fields and were therefore classified as resistant to dieback.

Characterization and genetic analysis of a lettuce (Lactuca sativa L.) mutant, weary, that exhibits reduced gravitropic response in hypocotyls and inflorescence stems.

A lettuce (Lactuca sativa L.) mutant that exhibits a procumbent growth habit was identified and characterized. In two wild type (WT) genetic backgrounds, segregation patterns revealed that the mutant phenotype was controlled by a recessive allele at a single locus, which was designated weary.

Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes.

We present here the first fully integrated, comprehensive map of the canine genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic information. We have mapped a collection of 266 chromosome-specific cosmid clones, each containing a microsatellite marker, to all 38 canine autosomes by fluorescence in situ hybridization (FISH). A 1500-marker RH map, comprising 1078 microsatellites, 320 dog gene markers, and 102 chromosome-specific markers, has been constructed using the RHDF5000-2 whole-genome radiation hybrid panel.

Mapping morphological genes relative to molecular markers in lettuce (Lactuca sativa L.).

Two F2 populations were generated by crossing morphologically diverse genetic stocks in order to map 10 morphological traits relative to polymerase chain reaction-based molecular markers (RAPDs). Using one segregating population generated from crossing the experimental line, 'dwarf-2', with the butterhead cultivar, 'Saffier', the dwarf phenotype conditioned by the dwf2 locus was mapped using bulked segregation analysis to within 38 cM of the Adh3 locus. Using the second segregating population generated by crossing two experimental lines, 87-25-1M x 87-109M, nine traits [white seed (w), brown seed (br), salmon flower colour (sa), pale yellow flower colour (pa), virescent juvenile leaf colour (vi), plump involucre (pl), yellow seed (y), one of two complementary genes for anthocyanin expression (C or G) and anthocyanin spotting (Rs)] were linked to RAPD loci, but only six of them could be placed on an existing genetic map of lettuce generated by analysis of cv.

Seven new linkage groups assigned to the DogMap reference families.

Twenty microsatellite markers have been typed on to the DogMap reference families, of which 18 were found to be polymorphic. One marker has been assigned to an existing linkage group and nine others have formed seven new linkage groups with previously typed markers. Only one of the new groups could be ordered.

First Report of Tomato Bushy Stunt Virus Isolated from Lettuce.

In recent years a disease causing dieback and necrosis of Romaine and leaf lettuce has become increasingly important in California and incidence is becoming more widespread. This disease has been primarily found in areas where soil has been dredged from a river or in flooded land. Tomato bushy stunt virus (TBSV) isolates have been isolated from roots and leaves of symptomatic lettuce.

FISH mapping and identification of canine chromosomes.

The karyotype of the domestic dog (Canis familiaris) is widely accepted as one of the most difficult mammalian karyotypes to work with. The dog has a total of 78 chromosomes; all 76 autosomes are acrocentric in morphology and show only a gradual decrease in length. Standardization of the canine karyotype has been performed in two stages.

DNA marker C04107 for copper toxicosis in a population of Bedlington terriers in the United Kingdom.

The DNA microsatellite marker C04107, linked to the Bedlington terrier copper toxicosis locus, is used diagnostically in the USA to detect the disease allele. This marker has been typed in Bedlington terriers of known disease status in the United Kingdom, and it is concluded that it should be useful in eradicating the disease from the breed in the UK. The marker also identified a dog which had been diagnosed on the basis of a liver biopsy as having the disease, as being unaffected; a second liver biopsy confirmed that the dog did not have copper toxicosis.

Von Wille-brand's disease in UK dobermanns: possible correlation of a polymorphic DNA marker with disease status.

Ninety-one dobermanns have been typed for a polymorphic microsatellite DNA marker situated within an intron of the von Willebrand factor gene and the alleles correlated with von Wille-brand's disease status. Two alleles were identified, one associated only with the normal gene and the other with both normal and disease genes.

Heterosynapsis and axial equalization of the sex chromosomes of the northern bobwhite quail.

The pairing behavior of the Z and W chromosomes in the female northern bobwhite quail (Colinus virginianus) was analyzed by electron microscopy of silver-stained synaptonemal complexes (SCs). After autosomal pairing was completed, synapsis of the sex chromosomes initiated at the short-arm end of the W chromosome and one end of the Z chromosome. Synapsis then progressed unidirectionally, producing a sex bivalent in which the entire length of the W axis was paired with an equivalent length of the Z axis.