Quantitative trait prediction based on SNP-array data, a simulation study.

Bioinformatics. 2011 Jan 31;

Authors: Yip WK, Lange C

MOTIVATION: Using simulation studies for quantitative trait loci, we evaluate the prediction quality of regression models that include as covariates SNPs which did not achieve genome-wide significance in the original genome-wide association study, but were among the SNPs with the smallest p-value for the selected association test. We compare the results of such regression models to the standard approach which is to include only SNPs that achieve genome-wide significance. Using mean square prediction error (MSPE) as the model metric, our simulation results suggest that by using the coefficient of determination (R(2)) value as a guideline to increase or reduce the number of SNPs included in the regression model, we can achieve better prediction quality than the standard approach. However, important parameters such as trait heritability, the approximate number of QTLs, etc have to be determined from previous studies or have to be estimated accurately.

PMID: 21285022 [PubMed - as supplied by publisher]

Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.

Blood. 2011 Feb 1;

Authors: Tiu RV, Gondek LP, O'Keefe CL, Elson P, Huh J, Mohamedali A, Kulasekararaj A, Advani AS, Paquette R, List AF, Sekeres MA, McDevitt MA, Mufti GJ, Maciejewski JP

Single nucleotide polymorphism arrays (SNP-A) have emerged as an important tool in the identification of chromosomal defects undetected by metaphase cytogenetics (MC) in hematologic cancers, offering superior resolution of unbalanced chromosomal defects and acquired copy-neutral loss of heterozygosity. Myelodysplastic syndromes (MDS) and related cancers share recurrent chromosomal defects and molecular lesions that predict outcomes. We hypothesized that combining SNP-A and MC could improve diagnosis/prognosis and further the molecular characterization of myeloid malignancies. We analyzed MC/SNP-A results from 430 patients (MDS=250, MDS/MPN=95, AML from MDS=85). The frequency and clinical significance of genomic aberrations was compared between MC and MC plus SNP-A. Combined MC/SNP-A karyotyping lead to higher diagnostic yield of chromosomal defects (74 vs. 44%, p=<0.0001), compared to MC alone, often through detection of novel lesions in patients with normal/non-informative (54%) and abnormal (62%) MC results. Newly detected SNP-A defects contributed to poorer prognosis for patients stratified by current morphologic and clinical risk schemes. The presence and number of new SNP-A detected lesions are independent predictors of overall and event free survival. The significant diagnostic and prognostic contribution of SNP-A-detected defects in MDS and related diseases underscores the utility of SNP-A when combined with MC in hematologic malignancies.

PMID: 21285439 [PubMed - as supplied by publisher]

500K SNP array analyses in blood and saliva showed no differences in a pair of monozygotic twins discordant for cleft lip.

Am J Med Genet A. 2011 Feb 22;

Authors: Jakobsen LP, Bugge M, Ullmann R, Schjerling CK, Borup R, Hansen L, Eiberg H, Tommerup N

PMID: 21344637 [PubMed - as supplied by publisher]

193 BOVINE EMBRYO GENOTYPING USING A 50K SINGLE NUCLEOTIDE POLYMORPHISM CHIP.

Reprod Fertil Dev. 2011 Jan;23(1):197

Authors: D Le Bourhis A, Mullaart E, Humblot P, Coppieters W, Ponsart C

Genomic tools are now available for most livestock species and are used routinely for marker-assisted selection (MAS) and genomic selection (GS) in cattle. Recently, multiple-marker detection has been achieved from biopsies of preimplantation stage embryos, thus allowing embryos to be selected before transfer (Le Bourhis et al. 2009 Reprod. Fertil. Dev. 21, 192 abst). This strategy provides the opportunity to estimate some traits of particular interest, the presence of genetic abnormalities, or both. The present work aimed to assess the efficiency of MAS/GS evaluation from biopsied bovine embryos by using the bovine 50K single nucleotide polymorphism (SNP) Illumina chip. A biopsy of 5 to 10 cells was obtained under laboratory conditions, using a microblade under a stereomicroscope, from 29 in vitro-cultured morulae and blastocysts. Biopsies were transferred individually as dry samples in tubes and sent frozen (n=13) or at room temperature (n=16) to the genotyping laboratory. The genomic DNA of each biopsy was amplified using a whole-genome amplification (WGA) kit according to the manufacturer's instructions (Qiagen REPLI-g(®) Mini Kit, Qiagen, Valencia, CA). Following WGA, DNA concentration was determined by using PicoGreen. For subsequent genotyping, a custom CRV 50K Illumina chip was used. Call rates were calculated from 50905 SNP. Percentage of allele drop-out (%ADO), which was estimated from the number of heterozygous markers [%ADO=(calculated hetero - observed hetero)/calculated hetero]. Parentage error was estimated from 12 embryos by using the genotypes of the parents of the embryos. Both groups of transport conditions were compared using Student's t-test. Results are presented as mean±SEM. A greater quantity of DNA was obtained after amplification of biopsies that were sent frozen to the laboratory when compared with those at room temperature (P<0.05). However, the SNP call rate, %ADO, and parentage error did not differ between groups. These results indicate that genotyping from embryo biopsies following WGA can be achieved with good efficiency when using high-density marker chips. To validate the use of MAS/GS from early embryos in breeding schemes, a larger number of in vivo embryos are currently genotyped under field conditions. This will allow the reliability of this method to be assessed and the correlation between embryo and calf genetic evaluation to be quantified with the current WGA efficiency.

PMID: 21367177 [PubMed - as supplied by publisher]