Comparative genetic mapping of cellular rel sequences in man, mouse, and the domestic cat.

We used in situ hybridization techniques to assign the human c-rel locus to the centromere-proximal portion of the short arm of chromosome 2 (2cent-2p13). We also determined the chromosomal location of c-rel sequences in the domestic cat and the laboratory mouse by using a human c-rel fragment to screen panels of rodent X cat and hamster X mouse somatic cell hybrid DNAs. The c-rel locus apparently maintains similar syntenic relationships with other known genetic markers in the human and cat, but displays different linkage relationships in the mouse.     

Molecular and genetic mapping of the mouse mdx locus

mdx is an X-linked muscular dystrophy mutant of the mouse and a putative homolog of the human X-linked muscular dystrophy locus--Duchenne muscular dystrophy (DMD). Utilizing a C57BL/10/Mus Spretus interspecific cross in which the mdx mutation was segregating, we have constructed a detailed genetic map around the mdx locus on the mouse X chromosome. We were unable to detect recombinants between mdx and exonic probes derived from the human DMD gene. These genetic data support the contention from biochemical studies (E.P. Hoffman, R. H. Brown, and L. M. Kunkel, 1987, Cell 51: 919-928) that DMD and mdx are homologous genes.     

Analysis of cell movements and fate mapping during early embryogenesis in Drosophila melanogaster

Four spatially differentiated surface regions, called aeropyle crown, flat, stripe, and micropyle, are found on the mature eggshell (chorion). Specializations of the apical surfaces of the secretory follicular epithelial cells are implicated in the formation of regional patterns on the chorion. Some of these specializations are restricted to cells overlying certain regions; others are shared by more than one region. Differences between regions are more apparent on the surface than within the bulk of the chorion. Evidence is presented that distinct cell populations, corresponding to the regions, are present long before the start of choriogenesis. One hundred eighty-six chorion-specific polypeptides have been resolved by two-dimensional gel electrophoresis. Fifteen of these are found entirely or predominantly in the aeropyle crown and stripe regions, while eight others are restricted to the aeropyle crown region. Certain of the spatially restricted components are quite unusual in their amino acid compositions when compared with previously analyzed chorion components. Others are closely related, although clearly distinct.     

Autosomal genetic diversity in non‐breed horses from eastern Eurasia provides insights into historical population movements

Many events in the history of eastern Eurasia, including the process of domestication itself, the initial spread of domestic horses and subsequent movements, are believed to have affected the genetic structure of domestic horse populations in this area. We investigated levels of within‐ and between‐population genetic diversity in ‘non‐breed horses’ (working horses sampled in remote areas) from 17 locations in Asia and parts of Eastern Europe, using 26 autosomal microsatellite loci. Non‐breed horses have not been subject to the same intensity of artificial selection and closed breeding as have most breed animals and are thus expected to better reflect the population history of domestic horses. Despite geographic distances of between 300 and 7000 km between sampling locations, pairwise F _ST was very low (range: <0.001 to ?0.033), suggesting historically high levels of gene flow. Our analyses of non‐breed horses revealed a pattern of isolation by distance and a significant decline in genetic diversity (expected heterozygosity and allelic richness) from east to west, consistent with a westward expansion of horses out of East Asia. Although the timing of this putative expansion is unclear, our results highlight the benefit of studying animals that do not belong to particular breeds when investigating aspects of a population's history.     

Neural control of breathing: insights from genetic mouse models.

Recent studies described the in vivo ventilatory phenotype of mutant newborn mice with targeted deletions of genes involved in the organization and development of the respiratory-neuron network. Whole body flow barometric plethysmography is the noninvasive method of choice for studying unrestrained newborn mice. Breathing-pattern abnormalities with apneas occur in mutant newborn mice that lack genes involved in the development and modulation of rhythmogenesis. Studies of deficits in ventilatory responses to hypercapnia and/or hypoxia helped to identify genes involved in chemosensitivity to oxygen and carbon dioxide. Combined studies in mutant newborn mice and in humans have shed light on the pathogenesis of genetically determined respiratory-control abnormalities such as congenital central hypoventilation syndrome, Rett syndrome, and Prader-Willi syndrome. The development of mouse models has opened up the field of research into new treatments for respiratory-control disorders in humans.     

Arthropod Hox genes: insights on the evolutionary forces that shape gene functions

Comparative studies suggest that gene duplication, changes in cis-regulatory elements and changes in protein sequence all contribute to the evolution of Hox gene functions, but the evolutionary dynamics of these changes are probably different. It seems likely that gene duplications arise as neutral changes and acquire an adaptive significance later on. By contrast, some changes in regulatory and protein-coding sequences can have immediate consequences in morphological evolution.     

High‐precision genetic mapping of behavioral traits in the diversity outbred mouse population

Historically our ability to identify genetic variants underlying complex behavioral traits in mice has been limited by low mapping resolution of conventional mouse crosses. The newly developed Diversity Outbred (DO) population promises to deliver improved resolution that will circumvent costly fine‐mapping studies. The DO is derived from the same founder strains as the Collaborative Cross (CC), including three wild‐derived strains. Thus the DO provides more allelic diversity and greater potential for discovery compared to crosses involving standard mouse strains. We have characterized 283 male and female DO mice using open‐field, light–dark box, tail‐suspension and visual‐cliff avoidance tests to generate 38 behavioral measures. We identified several quantitative trait loci (QTL) for these traits with support intervals ranging from 1 to 3 Mb in size. These intervals contain relatively few genes (ranging from 5 to 96). For a majority of QTL, using the founder allelic effects together with whole genome sequence data, we could further narrow the positional candidates. Several QTL replicate previously published loci. Novel loci were also identified for anxiety‐ and activity‐related traits. Half of the QTLs are associated with wild‐derived alleles, confirming the value to behavioral genetics of added genetic diversity in the DO. In the presence of wild‐alleles we sometimes observe behaviors that are qualitatively different from the expected response. Our results demonstrate that high‐precision mapping of behavioral traits can be achieved with moderate numbers of DO animals, representing a significant advance in our ability to leverage the mouse as a tool for behavioral genetics .     

Phylogenetic fate mapping: theoretical and experimental studies applied to the development of mouse fibroblasts

Mutations are an inevitable consequence of cell division. Similarly to how DNA sequence differences allow inferring evolutionary relationships between organisms, we and others have recently demonstrated how somatic mutations may be exploited for phylogenetically reconstructing lineages of individual cells during development in multicellular organisms. However, a problem with such "phylogenetic fate maps" is that they cannot be verified experimentally; distinguishing actual lineages within clonal populations requires direct observation of cell growth, as was used to construct the fate map of Caenorhabditis elegans, but is not possible in higher organisms. Here we employ computer simulation of mitotic cell division to determine how factors such as the quantity of cells, mutation rate, and the number of examined marker sequences contribute to fidelity of phylogenetic fate maps and to explore statistical methods for assessing accuracy. To experimentally evaluate these factors, as well as for the purpose of investigating the developmental origins of connective tissue, we have produced a lineage map of fibroblasts harvested from various organs of an adult mouse. Statistical analysis demonstrates that the inferred relationships between cells in the phylogenetic fate map reflect biological information regarding the origin of fibroblasts and is suggestive of cell migration during mesenchymal development.     

The Mycelium Blueprint: insights into the cues that shape the filamentous fungal colony

The mycelium is an organised cellular network that develops according to a functionally coherent plan. As it expands, the mycelium is capable of modulating the relative abundance of different cell types to suit the prevailing environmental conditions. This versatile pattern of multicellular development involves sophisticated environmental sensing and intercellular communication systems that have barely been recognised. This review describes an insight into our current understanding of the signalling molecules and mechanisms that take part in the ordered and timely emergence of various cell types and their biological significance. The prospects that this emerging knowledge may offer for the sustainable control of fungal colonisation or dispersal will also be considered.     

High‐density interspecific genetic linkage mapping provides insights into genomic incompatibility between channel catfish and blue catfish

Catfish is the leading aquaculture species in the United States. The interspecific hybrid catfish produced by mating female channel catfish with male blue catfish outperform both of their parent species in a number of traits. However, mass production of the hybrids has been difficult because of reproductive isolation. Investigations of genome structure and organization of the hybrids provide insights into the genetic basis for maintenance of species divergence in the face of gene flow, thereby helping develop strategies for introgression and efficient production of the hybrids for aquaculture. In this study, we constructed a high‐density genetic linkage map using the hybrid catfish system with the catfish 250K SNP array. A total of 26 238 SNPs were mapped to 29 linkage groups, with 12 776 unique marker positions. The linkage map spans approximately 3240 cM with an average intermarker distance of 0.25 cM. A fraction of markers (986 of 12 776) exhibited significant deviation from the expected Mendelian ratio of segregation, and they were clustered in major genomic blocks across 15 LGs, most notably LG9 and LG15. The distorted markers exhibited significant bias for maternal alleles among the backcross progenies, suggesting strong selection against the blue catfish alleles. The clustering of distorted markers within genomic blocks should lend insights into speciation as marked by incompatibilities between the two species. Such findings should also have profound implications for understanding the genomic evolution of closely related species as well as the introgression of hybrid production programs in aquaculture.     

Morphogenetic movements and multicellular development in the fruiting Myxobacterium, Stigmatella aurantiaca.

Stigmatella aurantiaca, strain DW-4, is a bacterium that grows as single cells in liquid culture but will synchronously aggregate and construct multicellular fruiting bodies when starved on an agar surface. The fruiting body consists of a stalk and several sporangia housing differentiated myxospores. Fruiting body development is stimulated by exposure of the aggregating cells to incandescent light.     

Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression

We have identified cDNAs clones for several cold-inducible mRNAs from the brown adipose tissue of mice. pCIN-1, a plasmid with a 900-base pair insert, encoded the mitochondrial uncoupling protein (UCP) as determined by the ability of the cDNA insert to select, by hybridization, an mRNA that could be translated into a 32,000-Da protein immunoprecipitable with anti-UCP antibodies. Nine tissues were analyzed; however, UCP cDNA hybridized to an mRNA species of 1.6 and 2.0 kilobase pairs only in brown adipose tissue. A maximum induction of 10-fold occurred within 6 h of exposure to cold (5 degrees C). A BamHI restriction fragment polymorphism detected by Southern blot analysis of genomic DNA in recombinant inbred mouse strains allowed us to map the UCP gene to Chromosome 8. The analysis of the UCP gene expression in diabetic (db) and obese (ob) mice maintained at 27 degrees C for 3 days followed by cold exposure for 4 h at 5 degrees C indicated that UCP mRNA levels in mutant mice were unaffected at 27 degrees C and only slightly reduced at 5 degrees C. Accordingly, the inability of diabetic and obese mice to thermoregulate is not associated with a lack of UCP mRNA induction.     

Stem-cell dynamics and lineage topology from in vivo fate mapping in the hematopoietic system

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A transgenic mouse that reveals cell shape and arrangement during ureteric bud branching

Understanding the cellular events that underlie epithelial morphogenesis is a key problem in developmental biology. Here, we describe a new transgenic mouse line that makes it possible to visualize individual cells specifically in the Wolffian duct and ureteric bud, the epithelial structures that give rise to the collecting system of the kidney. myr‐Venus, a membrane‐associated form of the fluorescent protein Venus, was expressed in the ureteric bud lineage under the control of the Hoxb7 promoter. In Hoxb7/myr‐Venus mice, the outlines of all Wolffian duct and ureteric bud epithelial cells are strongly labeled at all stages of urogenital development, allowing the shapes and arrangements of individual cells to be readily observed by confocal microscopy of freshly excised or cultured kidneys. This strain should be extremely useful for studies of cell behavior during ureteric bud branching morphogenesis in wild type and mutant mouse lines. genesis 47:61–66, 2009. © 2008 Wiley‐Liss, Inc.     

Joint‐linkage mapping and GWAS reveal extensive genetic loci that regulate male inflorescence size in maize

Both insufficient and excessive male inflorescence size leads to a reduction in maize yield. Knowledge of the genetic architecture of male inflorescence is essential to achieve the optimum inflorescence size for maize breeding. In this study, we used approximately eight thousand inbreds, including both linkage populations and association populations, to dissect the genetic architecture of male inflorescence. The linkage populations include 25 families developed in the U.S. and 11 families developed in China. Each family contains approximately 200 recombinant inbred lines (RILs). The association populations include approximately 1000 diverse lines from the U.S. and China. All inbreds were genotyped by either sequencing or microarray. Inflorescence size was measured as the tassel primary branch number (TBN) and tassel length (TL). A total of 125 quantitative trait loci (QTLs) were identified (63 for TBN, 62 for TL) through linkage analyses. In addition, 965 quantitative trait nucleotides (QTNs) were identified through genomewide study (GWAS) at a bootstrap posterior probability (BPP) above a 5% threshold. These QTLs/QTNs include 24 known genes that were cloned using mutants, for example Ramosa3 (ra3), Thick tassel dwarf1 (td1), tasselseed2 (ts2), liguleless2 (lg2), ramosa1 (ra1), barren stalk1 (ba1), branch silkless1 (bd1) and tasselseed6 (ts6). The newly identified genes encode a zinc transporter (e.g. GRMZM5G838098 and GRMZM2G047762), the adapt in terminal region protein (e.g. GRMZM5G885628), O‐methyl‐transferase (e.g. GRMZM2G147491), helix‐loop‐helix (HLH) DNA‐binding proteins (e.g. GRMZM2G414252 and GRMZM2G042895) and an SBP‐box protein (e.g. GRMZM2G058588). These results provide extensive genetic information to dissect the genetic architecture of inflorescence size for the improvement of maize yield.