Sequence-specific-oligonucleotides HLA determination from genomic DNA of myasthenic patients: Single locus analysis showed no association

Background. We test the hypothesis that the neuregulin 1 (NRG1) gene at chromosome 8p22-p12, which has been implicated as a susceptibility gene to schizophrenia, is associated with variations in schizotypal personality in non-clinical populations.Method. A randomly selected sample of 905 adolescents were assessed for their personality features using the Perceptual Aberration Scale (PAS) and the Schizotypal Personality Questionnaire (SPQ) and genotyped for three single nucleotide polymorphisms (SNP8NRG221533, rs3924999, and rs2954041) at the NRG1 gene. Relations between the three genetic variants and continuous schizotypal personality scores were evaluated using ANOVA for single-locus analyses and haplotype trend regression test for multi-locus analyses.Results. Single locus analysis showed that the A allele of rs3924999, a functional polymorphism in exon 2, had the largest effect size and exhibited a prominent allele–dose trend effect for the PAS score. Haplotype analyses using the haplotype trend regression test indicated that the A allele of rs3924999 was mainly responsible for the association with the PAS but not with the SPQ or its three factors, and the magnitude of significance was not strengthened by the combination of this allele with adjacent locus.Conclusions. Our study provides the first evidence for the association of NRG1 with schizotypal personality and indicates a possible role of NRG1 in the genetic etiology of schizophrenia through perceptual aberrations.

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Single Loci and Haplotypes in CAPN1 and CAST Genes are Associated with Growth, Biometrics, and in Vivo Carcass Traits in Santa Inês Sheep

Annals of Animal Science ◽

10.2478/aoas-2020-0007 ◽

2020 ◽

Vol 20 (2) ◽

pp. 465-483

Author(s):

Alessandro Lima Machado ◽

Ariana Nascimento Meira ◽

Evandro Neves Muniz ◽

Hymerson Costa Azevedo ◽

Luiz Lehmann Coutinho ◽

...

Keyword(s):

Body Length ◽

Average Daily Gain ◽

Carcass Traits ◽

Single Locus ◽

Additive Effects ◽

Body Depth ◽

Single Locus Analysis ◽

Fat Thickness ◽

Santa Inês ◽

Daily Gain

Abstractµ-calpain (CAPN1) and calpastatin (CAST) genes play key roles in protein turnover. The present study aimed to identify the variants in these genes associated with growth and ultrasound carcass traits in Santa Inês sheep. A sample of 192 no full sibling Santa Inês lambs was used. Fragments of the CAST and CAPN1 genes were amplified and next-generation sequencing was performed in the MiSeq platform. Variants in the CAPN1 and CAST sequences were then detected using bioinformatic tools. Withers and croup heights, body length, thoracic and croup widths, thoracic and leg girths, body depth, carcass fat score, rib eye area, fat thickness, body weights were recorded at weaning and at 140 days post-weaning, and average daily gain post-weaning was calculated. Both single-locus and haplotype association analyses were performed with the model as follows: farm (2 levels), year (4 levels), the month of birth (12 levels), and the covariate age of the animal. The fragments amplified included 4,514 bp between the 20th and 23rd exons of CAST as well as 3,927 bp between the 12th and 21st exons of CAPN1. In these regions, 58 (CAST) and 45 (CAPN1) variants were identified. In the CAST gene, the single-locus analysis revealed 22 suggestive additive effects (P<0.05) on several growth and carcass traits. Moreover, haplotype substitutions were associated with rib eye area (–0.689±0.290), average daily gain (–23.6±10.4), thoracic girth (–2.72±1.27), body length (–3.38±1.49), and leg girth (–2.84±1.37). Regarding the CAPN1 gene, the single-locus analysis identified seven suggestive additive effects, while only one haplotype replacement effect on fat thickness (–0.0143±0.0053) was detected. The results of the present study suggest that variants in the CAPN1 and CAST genes are associated with growth and ultrasound carcass traits in Santa Inês sheep, which may be a source of information to improve knowledge regarding the genetic control of these traits.

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Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651583 ◽

1993 ◽

Vol 69 (03) ◽

pp. 217-220 ◽

Cited By ~ 12

Author(s):

Jonathan B Rosenberg ◽

Peter J Newman ◽

Michael W Mosesson ◽

Marie-Claude Guillin ◽

David L Amrani

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Point Mutation ◽

Genomic Dna ◽

Comparative Sequence Analysis ◽

Chain Gene ◽

Molecular Defect ◽

Nucleotide Position ◽

Normal Individuals ◽

Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

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