Rapid Construction of a High-Density Rice Linkage Map by High Efficiency Genome Scanning (HEGS) System

High-density linkage maps are essential tools for genome analysis of various biological traits. Our developed compact multi-gel system, HEGS （high efficiency genome scanning） is a high-throughput and high-cost-performance electrophoresis apparatus. Using this system, a high-density （average interval 2.3 cM） map with 1 065 AFLP and 63 SSR markers was constructed from recombinant inbred lines of a japonica and indica hybrid in just two months of electrophoreses by a single person. More than 50% of the mapped AFLP markers were commonly polymorphic for several combinations between japonica and indica rice and 15% were applicable for genetically closer crosses between upland and lowland types of japonica rice. This system can be used for rapid analyses of all kinds of markers.

Genome scan of pigmentation traits in Friesian-Jersey crossbred cattle

Pigmentation traits expressed in animals are visual characteristics that allow us to distinguish between breeds and between strains within breed. The objective of this study was to map quantitative trait loci （QTLs） affecting the pigmentation traits in approximately 800 F2 grand daughter dairy cattle from a Holstein-Friesian and Jersey cross breed cattle. Traits analyzed included pigmentation phenotypes on the body, teat and hoop. The phenoypes were collected from digital photos or visual inspection of live animals. QTL mapping was implemented using half-sib and line-of-descent inheritance models. Our analysis initially detected a number of significant QTLs on chromosomes： 2, 6, 13, 15, 18 and 22. The significant QTLs were divided into two groups： one group influencing the pigmentation color and the other group affecting the absence or level of pigmentation. The most significant QTL peaks were observed on Bovine taurus autosome 18 （BTA18） close to melanocortin 1 receptor （MC1R） for the color traits, on BTA6 close to the receptor tyrosine kinase （K/T） and BTA22 close to microphthalmia-associated transcription factor （M/TF） gene for the spotting traits. Association studies were conducted for candidate regions or genes known to affect pigmentation in dairy cattle.

Efficient Haplotype Inference Algorithms in One Whole Genome Scan for Pedigree Data with Non-genotyped Founders

An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases where some pedigree founders are not genotyped, provided that for each nuclear family at least one parent is genotyped and each non-genotyped founder appears in exactly one nuclear family. The importance of this generalization lies in that such cases frequently happen in real data, because some founders may have passed away and their genotype data can no longer be collected. The algorithm runs in O（m^3n^3） time, where m is the number of single nucleotide polymorphism （SNP） loci under consideration and n is the number of genotyped members in the pedigree. This zero-recombination haplotyping algorithm is extended to a maximum parsimoniously haplotyping algorithm in one whole genome scan to minimize the total number of breakpoint sites, or equivalently, the number of maximal zero-recombination chromosomal regions. We show that such a whole genome scan haplotyping algorithm can be implemented in O（m^3n^3） time in a novel incremental fashion, here m denotes the total number of SNP loci along the chromosome.

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological,genetic and immunological data,we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease.It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation.Several genes have been so far related to the diagnosis of Crohn's disease.Those genes are related to innate pattern recognition receptors,to epithelial barrier homeostasis and maintenance of epithelial barrier integrity,to autophagy and to lymphocyte differentiation.So far,the most strong and replicated associations with Crohn's disease have been done with NOD2,IL23R and ATG16L1 genes.Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease.CARD15 seems not only a susceptibility gene,but also a disease-modifier gene for Crohn's disease.Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning

An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 com-plex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.

Genomic scanning enabling discovery of a new antibacterial bicyclic carbamate-containing alkaloid

Non-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical applications.Bacterial pyrrolizidine alkaloids(PAs),containing a scaffold of two fused five-membered ring system with a nitrogen atom at the bridgehead,have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates,followed by multistep oxidation,catalysed by single Bayer-Villiger(BV)enzymes,to yield PA scaffolds.Although bacterial PAs are rare in natural product inventory,bioinformatics analysis suggested that the biosynthetic gene clusters(BGCs)that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial genomes.However,most of the strains containing PA-like BGCs are not deposited in the public domain,therefore preventing further assessment of the chemical spaces of this group of bioactive metabolites.Here,we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome information.Among the strains tested,we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring formation.Subsequently one-strain-many-compound(OSMAC)method,supported by a combination of HR-MS,NMR,SMART 2.0 technology,and GNPS analysis,allowed identification and characterization of a new[5+7]heterobicyclic carbamate,legoncarbamate,together with five known PAs,bohemamine derivatives,from Streptomyces sp.CT37,a Ghanaian soil isolate.The absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD spectra.Legoncarbamate displays antibacterial activity against E.coli ATCC 25922 with an MIC value of 3.1μg/mL.Finally,a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.

Detecting polygenic selection in marine populations by combining population genomics and quantitative genetics approaches

Highly fecund marine species with dispersive life-history stages often display large population sizes and wide geographic distribution ranges. Consequently, they are expected to experience reduced genetic drift, efficient selection fueled by frequent adaptive mutations, and high migration loads. This has important consequences for understanding how local adaptation proceeds in the sea. A key issue in this regard, relates to the genetic architecture underlying fitness traits. Theory predicts that adaptation may involve many genes but with a high variance in effect size. Therefore, the effect of selection on allele frequencies may be substantial for the largest effect size loci, but insignificant for small effect genes. In such a context, the performance of population genomic methods to unravel the genetic basis of adaptation depends on the fraction of adaptive genetic variance explained by the cumulative effect of outlier loci. Here, we address some methodological challenges associated with the detection of local adaptation using molecular approaches. We provide an overview of genome scan methods to detect selection, including those assuming complex demographic models that better describe spatial population structure. We then focus on quantitative genetics approaches that search for genotype-phenotype associations at different genomic scales, including genome-wide methods evaluating the cumulative effect of variants. We argue that the limited power of single locus tests can be alleviated by the use of polygenic scores to estimate the joint contribution of candidate variants to phenotypic variation.

Studying the genetic basis of speciation in high gene flow marine invertebrates

A growing number of genes responsible for reproductive incompatibilities between species （barrier loci） exhibit the signals of positive selection. However, the possibility that genes experiencing positive selection diverge early in speciation and commonly cause reproductive incompatibilities has not been systematically investigated on a genome-wide scale. Here, I outline a research program for studying the genetic basis of speciation in broadcast spawning marine invertebrates that uses a priori genome-wide information on a large, unbiased sample of genes tested for positive selection. A targeted sequence capture approach is proposed that scores single-nucleotide polymorphisms （SNPs） in widely separated species populations at an early stage of allopatric divergence. The targeted capture of both coding and non-coding sequences enables SNPs to be characterized at known locations across the genome and at genes with known selective or neutral histories. The neutral coding and non-coding SNPs provide robust background distributions for identifying Fsm-outliers within genes that can, in principle, identify specific mutations experiencing diversifying selection. If natural hybridization occurs between species, the neutral coding and noncoding SNPs can provide a neutral admixture model for genomic clines analyses aimed at finding genes exhibiting strong blocks to introgression. Strongylocentrotid sea urchins are used as a model system to outline the approach but it can be used for any group that has a complete reference genome available.

Genomics Approaches to Domestication Studies of Horticultural Crops

The majority of crops we eat today are derived from the domestication of their wild progenitors. Crop domestication satisfies the human need for food and nutrition. Characterization of the history and genetic basis of crop domestication is essential for us to conduct modern breeding practices. Genomics provide unprecedented opportunities for us to study domestication. In this review, the typical domestication syndromes of horticultural crops will be introduced. Using the tomato as a typical example, we will discuss how genetic and genomic data were used to decipher the origins, progenitors, and domestication processes of this crop. In the domestication exploration of the genetic basis especially,genome-scaled diversity scanning approaches have gained great popularity. Combining these approaches with QTL(Quantitative trait locus)-mapping, GWAS(Genome wide association study), metabolomics and homology-based searches as well as pan-genomics have demonstrated tremendous advantages and significantly contribute to our understanding of domestication. Genomics studies will accelerate domestication research and further breeding of crops.

A novel candidate locus on chromosome 11p14.1-p11.2 for autosomal dominant hereditary spastic paraplegia

Background Hereditary spastic paraplegia （HSP） is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs. Thirteen loci for autosomal dominant HSP have been mapped. Methods A Chinese family with HSP was found in the Shandong province and Inner Mongolia Autonomous Region of China and genomic DNA of all 19 family members was isolated. After exclusion of known autosomal dominant loci, a genome wide scan and linkage analysis were performed. Results The known autosomal dominant loci of SPG3A, SPG4, SPG6, SPG8, SPG9, SPG10, SPG12, SPG13, SPG17, SPG19, SPG29, SPG31 and SPG33 were excluded by linkage analysis. The results of a genome wide scan demonstrated candidate linkage to a locus on chromosome 11 p14.1-p11.2, over an 18.88 cM interval between markers D11 S1324 and D11 S1933. A maximal, two point LOD score of 2.36 for marker D11S935 at a recombination fraction （e） of 0 and a multipoint LOD score of 2.36 for markers D11S1776, D11S1751, D11S1392, D11S4203, D11S935, D11S4083, and D11S4148 at θ=0, suggest linkage to this locus. Conclusion The HSP neuropathy in this family may represent a novel genetic entity, which will facilitate discovery of this causative gene.