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S Lien

Publications and source records attributed to S Lien.

At least 19 recordsLinked to original sources

Large Haplotypes Linked to Climate and Life History Variation in Divergent Lineages of Atlantic Salmon (Salmo salar).

Advances in sequencing are revealing that linked genomic architectures, enabling the evolution of co-adapted alleles at multiple loci, often shape complex phenotypes. Several recent studies have identified such architectures (e.g., chromosomal rearrangements and supergenes) contributing to adaptation or divergence across diverse species, from plants to mammals. Specifically, within Atlantic salmon (Salmo salar ), genomic studies are revealing large haplotypes and structural variants that may underpin local adaptation in the species. Using data from > 4000 individuals from 134 locations spanning the North Atlantic Ocean, we identify a large (~3 Mbp) genomic region on Ssa18 showing patterns of differentiation and linkage disequilibrium (LD) indicative of a large haplotype block containing three divergent haplotypes (herein A, B and C haplotypes). In Europe, haplotypes A and B were common, whereas A and C were more common within North America, suggesting a shared 'ancestral' A haplotype, with different continent-specific alternative haplotypes. Data support independent origins of divergent haplotypes in each continent, as well as signals of trans-oceanic introgression of haplotypes. Haplotype frequency is strongly associated with latitude, climate and life history (smolt age); however, the strength and direction of these relationships vary across continents. Overall, our analyses were consistent with other studies that identify chromosomal rearrangements; however, long-read sequence data did not find evidence of a structural variant, and instead an ancestral fusion may explain the formation and maintenance of the observed haplotypes. Our study contributes to ongoing efforts to understand the evolutionary role of linked genomic architecture in Atlantic salmon and its significance in salmonid diversification.

Climate Change

High-resolution gametic map of the sheep callipyge region: linkage heterogeneity among rams detected by sperm typing.

The callipyge locus (CLPG) causing muscular hypertrophy in domestic sheep has previously been mapped to the distal part of ovine chromosome 18. In this study, an accurate multipoint linkage map consisting of six microsatellite markers in this chromosomal region was constructed based on the analysis of 1145 single sperm cells. The best supported order of markers was OARHH47-ILSTS54-MCM38-CSSM18-IDVGA30-BM S1561. The log odds against the second most likely order, which has a reversal of the closely linked markers CSSM18 and IDVGA30, was 5.026. Sperm typing can be used to examine a large number of meioses in single individuals, and therefore, was exploited to study individual variability of recombination rate in rams of different callipyge genotypes. The results revealed statistically significant linkage heterogeneity among rams (P < 0.05) for marker interval OARHH47-CSSM18, with individual recombination fractions varying from 0.209 to 0.357.

Animals

Comparison of milk protein allele frequencies in Nordic cattle breeds.

Allele frequencies at four milk protein loci were studied in five modern and 17 old Nordic cattle breeds in order to reveal variants that are characteristic for these populations. The B allele of CSN3, which has been associated with improved manufacturing properties of milk, showed significantly lower frequencies in modern production breeds than in old breeds of interest for conservation purposes. Characteristic frequencies of CSN1S1 (C), CSN2 (A2) and CSN3 (B) were found in Icelandic cattle, Swedish Mountain cattle, Northern Finncattle and Western Fjord cattle, which indicate a common origin of these populations. Further comparisons of allele frequencies in old Nordic breeds suggest sorting of these breeds into two groups with a northern and southern geographic location.

Alleles

Combinatorial strategies for the discovery of novel protease specificities.

This article discusses proven and possible ways to generate novel cleavage specificities in serine proteases using combinatorial mutagenesis, compares the different ways of screening or selecting for desirable mutants, and examines the ways in which combinatorial substrate libraries can be used to gain a more comprehensive insight into protease cleavage preferences. The use of bacteriophage to display both combinatorial protease libraries and combinatorial substrate libraries will be discussed.

Evaluation Studies as Topic

Characterisation of porcine peroxisome proliferator-activated receptors gamma 1 and gamma 2: detection of breed and age differences in gene expression.

Two isoforms of peroxisome proliferator-activated receptor gamma (PPAR gamma) cDNAs, gamma 1 and gamma 2, have been isolated and characterised in swine. The relative expression of the two transcripts was studied by northern blot analysis using total RNA isolated from several porcine tissues taken at three different ages (day 1, after 5 weeks and at 100 kg weight). Hybridisation were carried out with two different probes, one binding to both PPAR gamma transcripts and the other being PPAR gamma 2 specific. Strongest hybridisation signals with the PPAR gamma probe binding both variants were detected in adipose tissues and spleen at all three ages, whereas only faint or no signals were detected in other tissues. The tissue distribution pattern of PPAR gamma 1 and gamma 2 suggests a modulation of tissue distribution for the two transcripts and obvious age and breed differences in gene expression in swine.

Adipose Tissue

Fitting genetic mapping functions based on sperm typing: results for three chromosomal segments in cattle.

Genetic mapping functions translate the observed recombination rate between two loci into the corresponding map distance in Morgan units. Different mapping functions give different weights to multiple crossing over and therefore lead to different results. This points out that not every function is best suited to fit a data set. The data used in this study originated from 2214 sperm from 37 Norwegian bulls, which were genotyped for 11 markers. The optimal functions for the chromosomes 6, 23 and the sex chromosome of cattle were derived using the maximum likelihood method, the likelihood ratio test and empirical discriminant analysis. It became apparent that for each chromosome a different function fitted the data best. These were the function of Rao et al. (Human Heredity 1977, 27, 99-104) with p = 0.63 for chromosome 6, the function of Goldgar & Fain (American Journal of Human Genetics 1988, 43, 38-45) with C0 = 0.42, C1 = 0.47, C2 = 0.07 and C3 = 0.04 for chromosome 23 and the function of Felsenstein (Genetics 1979, 91, 769-75) with K = 0.23 for the sex chromosome. The well known functions of Haldane (Journal of Genetics 1919, 8, 299-309) and Kosambi (Annals of Eugenics 1944, 12, 172-5) were shown to be suboptimal in most cases. A function is said to be multilocus feasible if the evaluation of the probability of all possible recombination events does not lead to negative values. The optimal function for chromosome 23 turned out to be multilocus feasible, whereas the functions for chromosome 6 and the sex chromosome were not. The choice of the correct mapping function is shown to have a considerable impact in mapping studies, when double recombinations have to be taken into account. Since there is no unique best mapping function, it is argued that it might be useful to use a simple parametric mapping function (like the one of Felsenstein 1979) and to estimate the respective parameter specifically for a given data set.

Animals

Characterisation of bovine peroxisome proliferator-activated receptors gamma 1 and gamma 2: genetic mapping and differential expression of the two isoforms.

In this report we describe the isolation and characterisation of the cDNAs encoding two isoforms of peroxisome proliferator-activated receptor gamma (PPAR gamma), gamma 1 and gamma 2, in cattle. The cDNA sequences show strong conservation with the corresponding sequences reported in other species. The distribution of PPAR gamma mRNAs in various bovine tissues was investigated using Northern blot analysis. The highest expression was detected in adipose tissue with about equal amounts of the both transcripts while a differential expression was found in other tissues investigated. PPAR gamma 1 was expressed at relatively high levels in bovine spleen and lung and to a lower extent in ovary, mammary gland, and small intestine. The amount of PPAR gamma 2 was apparently lower than that of PPAR gamma 1 in spleen, lung, and ovary. These results indicate a modulation of tissue distribution for the two transcripts in cattle. Using genetic linkage analysis we have also assigned the PPAR gamma gene to bovine chromosome 22.

Animals

Mapping of bovine FcgammaR (FCGR) genes by sperm typing allows extended use of human map information.

Polymorphic sites within the bovine FcgammaRI (FCGR1), FcgammaRII (FCGR2), and FcgammaRIII (FCGR3) genes were used for proximal mapping of these genes to bovine Chromosome (Chr) 3 (BTA3) with paternal half-sib families from Norwegian Cattle. A fine-structure genetic map of the region was obtained by the analysis of 288 sperm cells from three bulls that were heterozygous for the loci included in the study. No recombinants were observed between FCGR2 and FCGR3 (242 sperm cells). Considering FCGR2 and FCGR3 as a single locus, a three-point linkage analysis for [FCGR2/FCGR3], FCGR1, and INRA003 was carried out. The best-supported order of the loci was found to be INRA003-FCGR1-[FCGR2/FCGR3]. Map distances in a two-point linkage analysis were 10.3 cM between [FCGR2/FCGR3] and FCGR1, and 25.5 cM between FCGR1 and INRA003, respectively. This linkage mapping of the bovine FCGR gene family resembles the human situation where all FCGR genes are located at Chr 1 (HSA1), at position q21-q24. Moreover, the results locate the evolutionary breakpoint between HSA1q and BTA3 within the human 1q24 region.

Alleles

Evidence for individual and between-family variability of the recombination rate in cattle.

We have conducted a study based on single sperm typing in a family design to assess patterns of variability of the male recombination rate in cattle. 2214 sperm of 37 bulls were typed for 11 loci on bovine Chromosomes (Chrs) 6, 23, and the sex chromosomes. Statistically significant individual variability of the recombination rate was observed for one interval in the pseudoautosomal region (PAR) of the bovine sex chromosomes; one marker interval on bovine Chr 23 exhibited individual variability that was close to significance. Thirty-five of the bulls were members of six paternal halfsib groups, and highly significant variability between families was found for one interval in the PAR. This variability may be due to DNA sequence differences in the PAR or to a genetic control of the recombination activity in this region. It is demonstrated that differences in the recombination rate of the magnitude observed in the present study may have a considerable impact on the power of QTL mapping experiments as well as on the sustainability of marker-assisted selection strategies.

Animals

A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes.

Agouti and extension are two genes that control the production of yellow-red (phaeomelanin) and brown-black (eumelanin) pigments in the mammalian coat. Extension encodes the melanocyte-stimulating hormone receptor (MC1R) while agouti encodes a peptide antagonist of the receptor. In the mouse, extension is epistatic to agouti, hence dominant mutants of the MC1R encoding constitutively active receptors are not inhibited by the agouti antagonist, and animals with dominant alleles of both loci remain darkly pigmented. In the fox the proposed extension locus is not epistatic to the agouti locus. We have cloned and characterized the MC1R and the agouti gene in coat colour variants of the fox (Vulpes vulpes). A constitutively activating C125R mutation in the MC1R was found specifically in darkly pigmented animals carrying the Alaska Silver allele (EA). A deletion in the first coding exon of the agouti gene was found associated with the proposed recessive allele of agouti in the darkly pigmented Standard Silver fox (aa). Thus, as in the mouse, dark pigmentation can be caused by a constitutively active MC1R, or homozygous recessive status at the agouti locus. Our results, demonstrating the presence of dominant extension alleles in foxes with significant red coat colouration, suggest the ability of the fox agouti protein to counteract the signalling activity of a constitutively active fox MC1R.

Agouti Signaling Protein

Multipoint linkage map from sperm typing data.

Sperm typing makes it possible to construct accurate multipoint linkage maps based on a theoretically unlimited number of meioses. The high sperm number from single individuals enables the dissection of hyper-recombinant regions and presents an ideal situation for studying recombination rate variability in mammals. Of particular relevance for livestock is the fact that fine structure mapping of functional genes by sperm typing can be used to identify the breakpoints between conserved syntenic groups in different species. This is important for the extrapolation of positional information from the highly developed human map to the lower density maps in farm animals.

Animals

The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color determination.

The melanocyte-stimulating hormone (MSH) receptor has a major function in the regulation of black (eumelanin) versus red (phaeomelanin) pigment synthesis within melanocytes. We report three alleles of the MSH-receptor gene found in cattle. A point mutation in the dominant allele ED gives black coat color, whereas a frameshift mutation, producing a prematurely terminated receptor, in homozygous e/e animals, produces red coat color. The wild-type allele E+ produces a variety of colors, reflecting the possibilities for regulating the normal receptor. Microsatellite analysis, RFLP studies, and coat color information were used to localize the MSH-receptor to bovine Chromosome (Chr) 18.

Alleles

Associations between casein haplotypes and milk yield traits.

The genotyping of 13 sires and 250 of their sons for casein polymorphisms revealed 10 different haplotypes for Norwegian Cattle. Associations between haplotypes and yields of protein, milk, and fat were studied using a granddaughter design. Three subsets of data containing families with haplotypes 1, 5, and 10 were analyzed independently and denoted by analyses 1, 5, and 10, respectively. In addition, all sire families of all haplotypes were pooled and analyzed in analysis T. No associations were found between haplotypes and traits for milk yield in analyses 1, 10, and T. However, the null hypothesis of an equal effect within sire of bulls was rejected in analysis 5 for yields of protein and milk. The increase in protein yield associated with haplotype 5 ranged from 2.52 to 14.58 kg (from .09 to .51 phenotypic standard deviations). These results may indicate the presence of at least one quantitative trait locus in the region of the casein genes that affects protein yield of Norwegian Cattle. The findings were confirmed with a new analysis of two large sire families segregating haplotype 5 (analysis 5N).

Animals