Relationships between non-metric skeletal traits and cranial size and shape.

A long-standing controversy exists about the comparative utility of metric and non-metric traits as biological indicators in population studies. We hypothesize that the underlying scale which determines the presence or absence of a cranial non-metric trait is an expression of general and/or local size variation in the cranium. Therefore metric and non-metric traits will share a common developmental determination. The hypothesis implies that the underlying scale of a non-metric trait will be correlated with measures of cranial size and shape. Forty-eight cranial metric and twenty-five cranial non-metric traits were scored on the left side of adult male crania from four North American Indian populations. New threshold traits were generated for each non-metric trait by dichotomizing discriminant scores produced by discriminant function analysis. The discriminant analysis was performed using metric traits to discriminate between groups formed by non-metric trait presence or absence. Every non-metric trait tested was significantly correlated with its threshold trait in at least one population. The correlations were of moderate to high levels depending on the trait and population sample studied. This implies that metric and non-metric traits share a moderate to high degree of developmental determination. The cause of these correlations may lie in the common effects that growth and development of the soft tissue and functional spaces of the cranium exert on both metric and non-metric traits.     

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S‐402R wild‐type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild‐type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild‐type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S‐402R, 192Y‐402R and 192S‐402Q with a double‐variant 192Y‐402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.     

Analysis of the associations between polymorphisms in GNAS complex locus and growth, carcass and meat quality traits in pigs

Imprinted genes are interesting candidates for marker assisted selection in farm animals. One of them—GNAS complex locus is engaged in obesity pathogenesis in humans and mice. In our study, we identified new polymorphism in porcine GNAS gene (variable number of CT repeats, accession number: rs196952953) and found that this polymorphism is in linkage disequilibrum with GNAS AM490165:g.324C>T. Statistical analysis (GLM procedure), performed on 552 animals (Large White n = 258 and Landrace n = 269), revealed that deduced haplotypes and GNAS AM490165:g.324C>T are associated with growth performance and a few carcass traits, but not with feed intake. We observed significant additive effects of GNAS AM490165:g.324C>T genotype and haplotype 2 (C/278 bp) on test daily gain (TDG), average daily gain (ADG), number of days on test, age of the slaughter (P < 0.01) and FCR ratio (P < 0.05). Animals with two copies of C/278 haplotype had significantly higher: TDG, ADG, lower feed:gain ratio and faster reached the weight of 100 kg. When carcass traits were considered, significant associations between GNAS AM490165:g.324C>T polymorphism, haplotype 2 (C/278) and weight of ham with and without backfat and skin (WH) (WH2), length of the carcass, height and the width of the loin, meat percentage, weight of the main cuts were identified. The significant dominance effects of GNAS AM490165:g.324C>T polymorphism and haplotype 2 on WH and WH2 were observed (P < 0.05). When the two breeds were analyzed separately significant associations were observed for most of the traits in Landrace while in Large White the same trends were present but the differences were mostly not significant. Among meat quality traits we found significant association between haplotype and IMF content in Landrace (P < 0.03). Our results show for the first time that GNAS complex locus may modulate economically important traits in pigs.     

Strong association between cancer and genomic instability

After a first wave of radiation-induced chromosomal aberrations, a second wave appears 20–30 cell generations after radiation exposure and persists thereafter. This late effect is usually termed “genomic instability”. A better term is “increased genomic instability”. This effect has been observed in many cell systems in vitro and in vivo for quite a number of biological endpoints. The radiation-induced increase in genomic instability is apparently a general phenomenon. In the development of cancer, several mutations are involved. With increasing genomic instability, the probability for further mutations is enhanced. Several studies show that genomic instability is increased not only in the cancer cells but also in “normal” cells of cancer patients e.g. peripheral lymphocytes. This has for example been shown in uranium miners with bronchial carcinomas, but also in untreated head and neck cancer patients. The association between cancer and genomic instability is also found in individuals with a genetic predisposition for increased radiosensitivity. Several such syndromes have been found. In all cases, an increased genomic instability, cancer proneness and increased radiosensitivity coincide. In these syndromes, deficiencies in certain DNA-repair pathways occur as well as deregulations of the cell cycle. Especially, mutations are seen in genes encoding proteins, which are involved in the G₁/S-phase checkpoint. Genomic instability apparently promotes cancer development. In this context, it is interesting that hypoxia, increased genomic instability and cancer are also associated. All these processes are energy dependent. Some strong evidence exists that the structure and length of telomeres is connected to the development of genomic instability.     

Association between the ABO locus and hematological traits in Korean

ABSTRACT: BACKGROUND: Recently, genomewide association studies identified a pleiotropic gene locus, ABO, as being significantly associated with hematological traits. To confirm the effects of ABO on hematological traits, we examined the link between the ABO locus and hematological traits in Korean population-based cohorts. RESULTS: Six tagging SNPs for ABO were analyzed with regard to their effects on hematological traits [white blood cell count (WBC), red blood cell count (RBC), platelet (Plat), mean corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC)]. Linear regression analyses were performed, controlling for recruitment center, sex, and age as covariates. Of the 6 tagging SNPs, 3 (rs2073823, rs8176720, and rs495828) and 3 (rs2073823, rs8176717, and rs687289) were significantly associated with RBC and MCV, respectively (Bonferroni correction p-value criteria < 0.05/6 = 0.008). rs2073823 and a reported SNP (rs8176746), as well as rs495828 and a reported SNP (rs651007), showed perfect linkage disequilibrium status (r2s = 0.99). Of the remaining 3 SNPs (rs8176720, rs8176717 and rs687289), rs8176717 generated an independent signal with moderate p-value (= 0.045) when it was adjusted for by rs2073823 (the most significant SNP). We also identified a copy number variation (CNV) that was tagged by the SNP rs8176717, the minor allele of which correlated with the deletion allele of CNV. Our haplotype analysis indicated that the haplotype that contained the CNV deletion was significantly associated with MCV (beta +/- se = 0.363 +/- 0.118, p =2.09 x 10-3). CONCLUSIONS: Our findings confirm that ABO is one of the genetic factors that are associated with hematological traits in the Korean population. This result is notable, because GWASs fail to evaluate the link between a CNV and phenotype traits.     

The role of BAMBI in regulating adipogenesis and myogenesis and the association between its polymorphisms and growth traits in cattle

Molecular Biology Reports - Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein that affects the growth, development and muscle regeneration of the body...     

MyoD基因对肉牛胴体性状影响的分析

用PCR技术克隆到MyoD基因的第二内含子, 采用PCR-SSCP方法研究了3个黄牛品种(鲁西牛、晋喃牛、秦川牛)及4个杂交肉牛(夏洛莱×鲁西牛、安格斯×鲁西牛、利木赞×鲁西牛、西门塔尔×鲁西牛)群体MyoD基因的多态性, 并分析了基因位点多态性与肉牛肉质性状的相关性。实验结果,在国内首次扩增出肉牛MyoD基因的第二内含子的全部序列, 共261 bp。用SSCP方法检测到MyoD基因内含子2有A和B两个等位基因。测序结果表明该座位的多态性是由于内含子二39 bp处C-T的突变和112 bp处C→G的突变造成的。等位基因B在中国地方品种的分布频率高于引进品种的杂交牛群体。c2检验的结果表明, 在该位点的除夏洛莱和安格斯杂交牛外, 其余五个群体(晋南、鲁西、秦川、西门塔尔杂交牛和利木赞杂交牛)均处于Hardy-Weinberg不平衡状态(P>0.05)。实验群体不同基因型与肉牛的宰前活重、胴体重、净肉重、高档肉重、眼肌面积等性状的影响差异极显著或显著(P<0.01或P<0.05), 并且AA型个体均高于AB型个体。     

Association between leptin gene polymorphisms and growth traits in Limousin cattle

A total of 129 Limousin calves were used to investigate how leptin gene polymorphisms affect growth traits, such as body weight, average daily gain, wither height, sacrum height and chest girth in beef cattle. Two single nucleotide polymorphisms (SNPs) were genotyped, including the Sau3AI polymorphism in intron 2 and the A59V polymorphism in exon 3. The genotype and allele frequencies for each SNP and the haplotype frequencies for both SNPs were estimated in the studied herd. Statistical analysis revealed that the A59V polymorphism significantly affected the body weight at 210 days of age (P ≤ 0.01) and the average daily gain between 3 and 210 days of age (P ≤ 0.05) with T as a desirable allele. No associations were observed between the Sau3AI polymorphism and the growth traits mentioned above. However, the average daily gain between 3 and 210 days of age was significantly higher in the CT/CT haplotype animals compared with the CC/CC and CC/CT individuals. These results indicated that selection for the A59V TT animals might contribute to an improved body weight in Limousin cattle. The article is published in the original.     

Strong associations between RFLP and protein polymorphisms for CD46

Human CD46 (membrane cofactor protein) is a cell surface glycoprotein with cofactor activity for the factor I mediated cleavage of components C3b and C4b. Using a CD46 cDNA clone, three restriction enzymes give simple two allele restriction fragment length polymorphisms (RFLPs) in samples of over 300 Caucasians. For Pvu II, P1 with a 16.5 kilobase (kb) fragment and P2 with 14.8 kb + 1.9 kb fragments have frequencies of .40 and .60. For Hin dIII, H1 with a 4.3 kb fragment and H2 with a 2.3 kb fragment have similar frequencies. For Bgl. II, B1 with a 10 kb fragment and B2 with 8.3 kb + 1.8 kb fragments have frequencies of 0.08 and 0.92. There is strong linkage disequilibrium between these polymorphic sites. Designating haplotypes by Hin dIII, Pvu II, Bgl II alleles, there are two common haplotypes P2, H2, B2 and P1, H1, B2, expected at frequencies of .6 and .32, one less common haplotype P1, H1, B1 expected at a frequency .08. The two major protein isoforms of CD46, as detected on peripheral blood lymphocytes by western blot, of M _r 66 000 () and 56 000 () are determined by differential splicing in production of the mRNA. A strong association between protein isoform and RFLP haplotypes in 30 unrelated subjects suggests that the splicing preference site is in linkage disequilibrium with the RFLPs. The results are consistent with haplotypes P2, H2, B2 and P1, H1, B1 producing predominantly ; P1, H1, B2 producing predominantly in about 72% of cases and in 28% of cases. Address correspondence and offprint requests to: A. Wilton, at the present address.     

Multiple locus genome-wide association studies for important economic traits of oil palm

Palm oil has a balanced fatty acid composition and has no trans fat. As a result, its use in food has increased as food-labeling laws have changed to specify trans fat content. Increasing oil production is the main goal in oil palm breeding. Genetic mapping and genomic studies in palm trees are necessary to understand the genetic architecture of economic traits of importance for palm oil production. To help achieve this, we sampled 422 oil palms from MPOB (Malaysian Palm Oil Board)­Angola germplasm collection and measured 13 economic traits from these palms. Multi-locus genome-wide association studies (GWAS) were conducted using least absolute shrinkage and selection operator (LASSO) and genome-wide efficient mixed model analysis. We identified 19 quantitative trait loci (QTLs) for 8 traits. Of these, four Angola-specific QTLs associated with bunch components were detected on chromosomes 4, 8, and 11. These QTLs are potentially useful for introgression of desirable genes from the Angola palms to advanced breeding populations for improvement of bunch and oil yield traits. The majority of the QTLs were detected by LASSO-A, in which the p values of individual markers were calculated based on bootstrapped standard errors. Many of the detected QTLs are nearby known QTLs detected from linkage studies reported by other research groups. We also conducted genomic selection (GS) for the 13 traits and concluded that GS can be an effective tool for oil palm breeding. This is the first GWAS and GS study conducted on oil palm germplasm from Angola, and the results can be very useful in oil palm genetic studies and breeding.     

Strong association between pseudogenization mechanisms and gene sequence length

 

Bacteriocins are peptide antibiotics from ribosomally translated precursors, produced by bacteria often through extensive post-translational modification. Minimal sequence conservation, short gene lengths, and low complexity sequence can hinder bacteriocin identification, even during gene calling, so they are often discovered by proximity to accessory genes encoding maturation, immunity, and export functions. This work reports a new subfamily of putative thiazole-containing heterocyclic bacteriocins. It appears universal in all strains of Bacillus anthracis and B. cereus, but has gone unrecognized because it is always encoded far from its maturation protein operon. Patterns of insertions and deletions among twenty-four variants suggest a repeating functional unit of Cys-Xaa-Xaa.

Reviewers

This article was reviewed by Andrei Osterman and Lakshminarayan Iyer.     

Strong association between pseudogenization mechanisms and gene sequence length

   

Pseudogenes arise from the decay of gene copies following either RNA-mediated duplication (processed pseudogenes) or DNA-mediated duplication (nonprocessed pseudogenes). Here, we show that long protein-coding genes tend to produce more nonprocessed pseudogenes than short genes, whereas the opposite is true for processed pseudogenes. Protein-coding genes longer than 3000 bp are 6 times more likely to produce nonprocessed pseudogenes than processed ones.     

Characterization of porcine leptin receptor polymorphisms and their association with reproduction and production traits

Fatness in pigs is of prime economic importance due to market incentives for production of lean pork and elevated fatness increasing the feed costs. Leptin (LEP) action, mediated through its specific receptors (LEPR), was reported to be involved in the regulation of fatness via feed intake, energy expenditure, and whole-body energy balance in pigs. In this study, we have designed 17 primer sets based on the human and mouse LEPR sequences and successfully amplified coding regions of 15 porcine LEPR exon fragments by polymerase chain reactions (PCR). Four single nucleotide polymorphisms (SNP) of Intron 2, Exons 2, 6, and 18 were found in Landrace, Yorkshire, and Duroc by mutagenetically separated-PCR (MS-PCR) and PCR-restriction fragment length polymorphisms (PCR-RFLP). Chi-square statistics was used to calculate homogeneity of genotypic frequencies of 4 gene polymorphisms for three breeds of animals. Effects of Intron 2, Exon 2, and Exon 18 polymorphisms on the reproduction trait such as litter sizes of sows were evident (p < 0.05) in Duroc and Yorkshire. There was no (p > 0.05) significant influence on the production trait of average daily gain due to four candidate gene polymorphisms in three porcine breeds. However, effects of Exon 6 and 18 polymorphisms on the production trait of backfat thickness were significant (p < 0.05) in Landrace and Yorkshire, respectively. Effects of Exon 18 polymorphisms on feed efficiency were also evident (p < 0.05) in Duroc.     

Characterization of swine adiponectin and adiponectin receptor polymorphisms and their association with reproductive traits

In this study, polymorphisms in genes encoding porcine adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) were evaluated for associations with reproductive traits in a Landrace sow population. Sixteen SNPs were identified, and among these, associations were found between reproductive traits and five SNPs. Heterozygous multiparous females for SNP ADIPOQEF601160:c.178G>A had fewer stillborn piglets (P < 0.05) and shorter weaning-to-oestrus intervals (P < 0.05). Multiparous females bearing the mutant allele for SNP ADIPOQEF601160:c.*1094_1095insC gave birth to fewer stillborn piglets (P < 0.05). In addition, selection for the ADIPOQ [A;C] haplotype is expected to result in multiparous sows having the lowest number of stillborn piglets and shorter weaning-to-oestrus intervals. In second-parity sows, the polymorphism in ADIPOR1 (AY856513:c.*129A>C) showed significant associations with live-born (P < 0.01) and stillborn (P < 0.05) piglets. In multiparous sows, a significant association was observed for an ADIPOR2 polymorphism (AY856514:c.*112G>A), with the c.*112GA genotype associated with shorter weaning-to-oestrus intervals (P < 0.01). Haplotype analyses of ADIPOR2 SNPs revealed that selection in favour of the [A;C] haplotype and against the [G;G] haplotype may result in sows having an increased number of live-born piglets and shorter weaning-to-oestrus intervals. We have therefore described specific SNPs and haplotypes that are associated with large litter size, fewer stillborn and mummified piglets and shorter weaning-to-oestrus intervals. Selection for these SNPs and haplotypes is a strategy to improve reproductive success in pigs.     

Replication of association between ADAM33 polymorphisms and psoriasis

Polymorphisms in ADAM33, the first gene identified in asthma by positional cloning, have been recently associated with psoriasis. No replication study of this association has been published so far. Data available in the French EGEA study (Epidemiological study on Genetics and Environment of Asthma, bronchial hyperresponsivensess and Atopy) give the opportunity to attempt to replicate the association between ADAM33 and psoriasis in 2002 individuals. Psoriasis (n = 150) has been assessed by questionnaire administered by an interviewer and a sub-sample of subjects with early-onset psoriasis (n = 74) has been identified based on the age of the subjects at time of interview (<40 years). Nine SNPs in ADAM33 and 11 SNPs in PSORS1 were genotyped. Association analysis was conducted by using two methods, GEE regression-based method and a likelihood-based method (LAMP program). The rs512625 SNP in ADAM33 was found associated with psoriasis at p = 0.01, the usual threshold required for replication (OR [95% CI] for heterozygotes compared to the reference group of homozygotes for the most frequent allele = 0.61 [0.42;0.89]). The rs628977 SNP, which was not in linkage disequilibrium with rs512625, was significantly associated with early-onset psoriasis (p = 0.01, OR [95% CI] for homozygotes for the minor allele compared to the reference group = 2.52 [1.31;4.86]). Adjustment for age, sex, asthma and a PSORS1 SNP associated with psoriasis in the EGEA data did not change the significance of these associations. This suggests independent effects of ADAM33 and PSORS1 on psoriasis. This is the first study that replicates an association between genetic variants in ADAM33 and psoriasis. Interestingly, the 2 ADAM33 SNPs associated with psoriasis in the present analysis were part of the 3-SNPs haplotypes showing the strongest associations in the initial study. The identification of a pleiotropic effect of ADAM33 on asthma and psoriasis may contribute to the understanding of these common immune-mediated diseases.     

Ovine insulin induced-gene-2: molecular characterization,polymorphisms and association with milk traits

The aim was to characterize the INSIG-2 gene in Sarda sheep and to highlight associations between polymorphisms and milk traits. Two-hundred ewes, in their third or fourth lactation who lambed a single lamb between 20th and 30th of November, were chosen. Monthly individual milk yield was recorded and from each ewe a sample of milk was taken to analyze fat and protein content. PCR–RFLP and DNA sequencing were carried out to detect polymorphisms. Five exons have been characterized and five mutations have been found G88A, 436TCAGdel, A471G, C1071T and T1737G all in the intronic regions. The ovine sequence and related variations were deposited in GenBank with accession number JX843812.1. The animals carrying AA genotype at position 88 showed a lower milk fat concentration than those with the AG or GG genotype (P < 0.05). A lower milk fat concentration was registered also in the animals with the TCAG deletion in position 436 (P < 0.05) and in the animals carrying AA genotype at position 471 compared to those with the AG or GG genotype (P < 0.05). Moreover, the animals carrying CC genotype at position 1071 had a greater milk yield than those with CT or TT genotype (P < 0.05) while ewes with TT genotype showed a higher milk protein concentration compared to the others (P < 0.05). A total of 11 haplotypes were detected but no significant associations with milk traits were found. In conclusion for the first time the complete coding sequence of INSIG-2 gene and its association with milk trait has been reported in this study.     

Characterization of swine leptin (LEP) polymorphisms and their association with production traits

Four polymorphisms in the swine leptin (LEP) gene were characterized and evaluated for association with economically important production traits in Yorkshire, Landrace and Duroc pigs. Our results show that these polymorphisms are generally of low frequency or are absent in pig populations. Two polymorphisms (A2845T and T3469C) may be associated (P < 0.0078) with feed intake and growth rate traits in Landrace pigs.