Hasil untuk "Genetics"

H. Kearney, E. Thorland, Kerry K. Brown et al.

C. Guthrie, G. Fink

J. Roughgarden

D. Wallace

A. Hoffmann, P. Parsons

H. Harris, D. Hopkinson, M. Duras

M. W. Young, S. Kay

Jeanne Amiel, S. Lyonnet

A. Vignal, D. Milan, M. Sancristobal et al.

During the last ten years, the use of molecular markers, revealing polymorphism at the DNA level, has been playing an increasing part in animal genetics studies. Amongst others, the microsatellite DNA marker has been the most widely used, due to its easy use by simple PCR, followed by a denaturing gel electrophoresis for allele size determination, and to the high degree of information provided by its large number of alleles per locus. Despite this, a new marker type, named SNP, for Single Nucleotide Polymorphism, is now on the scene and has gained high popularity, even though it is only a bi-allelic type of marker. In this review, we will discuss the reasons for this apparent step backwards, and the pertinence of the use of SNPs in animal genetics, in comparison with other marker types.

A. Wilson, R. Cann, R. Cann et al.

L. Bertram, C. Lill, R. Tanzi

E. Fearon

F. Soubrier, W. Chung, R. Machado et al.

R. Plenge, E. Scolnick, D. Altshuler

S. Manel, R. Holderegger

L. Pasqualucci, Hossein Khiabanian, Marco Fangazio et al.

Follicular lymphoma (FL) is an indolent disease, but 30%-40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, we show here that the dominant clone of FL and transformed FL (tFL) arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and antiapoptotic genes are introduced early in the common precursor, whereas tFL is specifically associated with alterations deregulating cell-cycle progression and DNA damage responses (CDKN2A/B, MYC, and TP53) as well as aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.

J. Flint, K. Kendler

Major depression is the commonest psychiatric disorder and in the U.S. has the greatest impact of all biomedical diseases on disability. Here we review evidence of the genetic contribution to disease susceptibility and the current state of molecular approaches. Genome-wide association and linkage results provide constraints on the allele frequencies and effect sizes of susceptibility loci, which we use to interpret the voluminous candidate gene literature. We consider evidence for the genetic heterogeneity of the disorder and the likelihood that subtypes exist that represent more genetically homogenous conditions than have hitherto been analyzed.

Ezanee Azlina Mohamad Hanif, Nurul Nadiah Ahmad Daud, Afreena Afiqah Azman

Abstract The heterogeneity in triple-negative breast cancer (TNBC) is one of the classical characteristics that contribute to its aggressiveness. The absence of oestrogen, progesterone, and low expression of HER2 receptors making chemotherapy is the only therapeutic mainstay in TNBC. Displaying high sensitivity to chemotherapy, disease recurrence is often a common event in TNBC patients too. Transforming Growth Factor β (TGFβ) is a growth factor ligand that releases cytokines highly reported in TNBC progression and response to drugs. The distinctive roles of molecular mechanisms in TNBC development between TGFβ isoforms are not fully established. Therefore, this study aimed to elucidate the cryptic intra-tumoral transcriptomic characteristics of each isoform (TGFβ1, TGFβ2, TGFβ3) from publicly available TNBC GEO datasets (GSE58812, GSE76124, GSE83937, and GSE95700). A total of 486 TNBC samples were stratified to represent TGFβ1-high versus TGFβ1-low, TGFβ2-high versus TGFβ2-low, and TGFβ3-high versus TGFβ3-low. The differential gene expression analysis showed distinct genes being expressed downstream to each isoform (TGFβ1-high–573 genes; TGFβ2-high–41 genes; TGFβ3-high–36). Interestingly, gene ontology and pathway analysis exhibited similar enrichment of the metabolic, cellular polarity, and Rap1 signalling pathways, all of which play critical roles in cancer progression through interplay crosstalk, represented in all isoforms. Some of the highlighted gene signatures were shown to possess clinical relevance in TNBC samples; each represents either protective or poorer prognostic effects, delineating potential targetable genes with diagnostic and prognostic values. This data offers a platform to explore further the roles of each isoform for better stratifying TNBC patients for treatment invention strategies.

Philibert Courau, Amaury Lambert, Emmanuel Schertzer

Modelling the evolution of a continuous trait in a biological population is one of the oldest problems in evolutionary biology, which led to the birth of quantitative genetics. With the recent development of GWAS methods, it has become essential to link the evolution of the trait distribution to the underlying evolution of allelic frequencies at many loci, co-contributing to the trait value. The way most articles go about this is to make assumptions on the trait distribution, and use Wright's formula to model how the evolution of the trait translates on each individual locus. Here, we take a gene's eye-view of the system, starting from an explicit finite-loci model with selection, drift, recombination and mutation, in which the trait value is a direct product of the genome. We let the number of loci go to infinity under the assumption of strong recombination, and characterize the limit behavior of a given locus with a McKean-Vlasov SDE and the corresponding Fokker-Planck IPDE. In words, the selection on a typical locus depends on the mean behaviour of the other loci which can be approximated with the law of the focal locus. Results include the independence of two loci and explicit stationary distribution for allelic frequencies at a given locus (under some assumptions on the fitness function).