Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism differentially predicts hippocampal function in medication-free patients with schizophrenia.

Mol Psychiatry. 2013 Jan 15;

Authors: Eisenberg DP, Ianni AM, Wei SM, Kohn PD, Kolachana B, Apud J, Weinberger DR, Berman KF

Abstract
A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val(66)Met SNP and [(15)O]H(2)O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working memory-related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions.Molecular Psychiatry advance online publication, 15 January 2013; doi:10.1038/mp.2012.187.

PMID: 23319002 [PubMed - as supplied by publisher]

A 34K SNP genotyping array for Populus trichocarpa: Design, application to the study of natural populations and transferability to other Populus species.

Mol Ecol Resour. 2013 Jan 11;

Authors: Geraldes A, Difazio SP, Slavov GT, Ranjan P, Muchero W, Hannemann J, Gunter LE, Wymore AM, Grassa CJ, Farzaneh N, Porth I, McKown AD, Skyba O, Li E, Fujita M, Klápště J, Martin J, Schackwitz W, Pennacchio C, Rokhsar D, Friedmann MC, Wasteneys GO, Guy RD, El-Kassaby YA, Mansfield SD, Cronk QC, Ehlting J, Douglas CJ, Tuskan GA

Abstract
Genetic mapping of quantitative traits requires genotypic data for large numbers of markers in many individuals. For such studies, the use of large single nucleotide polymorphism (SNP) genotyping arrays still offers the most cost-effective solution. Herein we report on the design and performance of a SNP genotyping array for Populus trichocarpa (black cottonwood). This genotyping array was designed with SNPs pre-ascertained in 34 wild accessions covering most of the species latitudinal range. We adopted a candidate gene approach to the array design that resulted in the selection of 34 131 SNPs, the majority of which are located in, or within 2 kb of, 3543 candidate genes. A subset of the SNPs on the array (539) was selected based on patterns of variation among the SNP discovery accessions. We show that more than 95% of the loci produce high quality genotypes and that the genotyping error rate for these is likely below 2%. We demonstrate that even among small numbers of samples (n = 10) from local populations over 84% of loci are polymorphic. We also tested the applicability of the array to other species in the genus and found that the number of polymorphic loci decreases rapidly with genetic distance, with the largest numbers detected in other species in section Tacamahaca. Finally, we provide evidence for the utility of the array to address evolutionary questions such as intraspecific studies of genetic differentiation, species assignment and the detection of natural hybrids.

PMID: 23311503 [PubMed - as supplied by publisher]

Contribution of domestic production records, Interbull estimated breeding values, and single nucleotide polymorphism genetic markers to the single-step genomic evaluation of milk production.

J Dairy Sci. 2013 Jan 9;

Authors: Přibyl J, Madsen P, Bauer J, Přibylová J, Simečková M, Vostrý L, Zavadilová L

Abstract
Estimated breeding values (EBV) for first-lactation milk production of Holstein cattle in the Czech Republic were calculated using a conventional animal model and by single-step prediction of the genomic enhanced breeding value. Two overlapping data sets of milk production data were evaluated: (1) calving years 1991 to 2006, with 861,429 lactations and 1,918,901 animals in the pedigree and (2) calving years 1991 to 2010, with 1,097,319 lactations and 1,906,576 animals in the pedigree. Global Interbull (Uppsala, Sweden) deregressed proofs of 114,189 bulls were used in the analyses. Reliabilities of Interbull values were equivalent to an average of 8.53 effective records, which were used in a weighted analysis. A total of 1,341 bulls were genotyped using the Illumina BovineSNP50 BeadChip V2 (Illumina Inc., San Diego, CA). Among the genotyped bulls were 332 young bulls with no daughters in the first data set but more than 50 daughters (88.41, on average) with performance records in the second data set. For young bulls, correlations of EBV and genomic enhanced breeding value before and after progeny testing, corresponding average expected reliabilities, and effective daughter contributions (EDC) were calculated. The reliability of prediction pedigree EBV of young bulls was 0.41, corresponding to EDC = 10.6. Including Interbull deregressed proofs improved the reliability of prediction by EDC = 13.4 and including genotyping improved prediction reliability by EDC = 6.2. Total average expected reliability of prediction reached 0.67, corresponding to EDC = 30.2. The combination of domestic and Interbull sources for both genotyped and nongenotyped animals is valuable for improving the accuracy of genetic prediction in small populations of dairy cattle.

PMID: 23312993 [PubMed - as supplied by publisher]

R620W polymorphism of protein tyrosine phosphatase PTPN22 in Egyptian children and adolescents with systemic lupus erythematosus: relation to thyroid autoimmunity.

Int J Adolesc Med Health. 2013 Jan 12;:1-7

Authors: Hamza RT, Awwad KS, Temsah KA, Hamed AI

Abstract
Abstract Background: Some studies showed associations of the minor T allele of the C1858T single nucleotide polymorphism (SNP) corresponding to the R620W amino acid substitution of protein tyrosine phosphatase (PTPN22) with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). Objectives: To study the frequency of PTPN22 R620W polymorphism among Egyptian patients with SLE and to test the association of the T allele with autoimmune thyroid disease in such patients. Methods: Clinical evaluation, measurement of thyroid hormones and antibodies, and genotyping of PTPN22 R620W polymorphism were done for 60 SLE patients and 60 age- and sex-matched healthy subjects. Results: Nineteen SLE cases (31.67%) had thyroid dysfunction with subclinical hypothyroidism being the most frequent form of thyroid dysfunction (20%) followed by primary hypothyroidism (6.67%), subclinical hyperthyroidism (3.33%) and primary hyperthyroidism (1.67%). Autoimmune thyroid disease was detected in 36.67% of cases. Systemic lupus erythematosus disease activity index (SLEDAI) score did not differ between patients with thyroid dysfunction and euthyroid patients (p=0.061) nor with the frequency of positive thyroid peroxidise antibodies (TPOAb, p=0.092) and antithyroglobulin antibodies (ATGAb, p=0.1). T allele frequency did not differ between cases and controls (p=1.19) and was associated with autoimmune thyroid disease in Egyptian SLE patients (p=0.002). Conclusions: R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility among Egyptian SLE patients but appears to be a risk factor for concurrent autoimmune thyroid disease and SLE.

PMID: 23314521 [PubMed - as supplied by publisher]