Highest Logarithm Of Odds Research Articles

QSUB2: A novel QTL with positive epistasis with SUB1 locus enhances submergence tolerance in rice

AbstractClimate change is expected to significantly increase submergence stress of lowland rice (Oryza sativa) production in Africa. There is a need to further improve the ability of SUB1 gene to tolerate submergence stress. Genetic control of submergence tolerance was studied in a moderately tolerant to submergence African rice landrace “TOS6454.” Three mapping populations with a total of 1182 lines were developed by crossing TOS6454 with three popular rice varieties of West Africa that are high‐yielding but submergence susceptible, that is, FARO44, FARO52, and FARO60. The screening for submergence was conducted at the Africa Rice Center (AfricaRice) station in Ibadan, Nigeria during 2016–2018. The three mapping populations were genotyped with single nucleotide polymorphic markers either on the Kompetitive allele specific PCR or the DArTseq platforms. Quantitative trait locus (QTL) analysis revealed five different QTLs on chromosomes 1, 2, 3, 4, and 9. The QTLs on chromosomes 2 (qSUB2) and 9 (qSUB9) had consistent large effects and the tolerance alleles were contributed by TOS6454. The QTL on chromosome 9 (qSUB9) had a large effect on submergence tolerance in all three mapping populations. This QTL had a highest logarithm of odds (LOD) score of 30.46 and explained as much as 27.7% phenotypic variation (R2), with an additive effect of up to 9.39. The QTL on chromosome 2 (qSUB2) had a highest LOD score of 10.78 and explained up to 10.8% R2 for this trait. Furthermore, qSUB2 had positive epistasis with qSUB9 which further increased submergence tolerance. A total of 57 lines carrying both qSUB2 and qSUB9 alleles were superior to all other lines in submergence tolerance. qSUB9 co‐segregated with ART5 a marker for the SUB1 gene; thus, it is suggested that qSUB9 is the same as the well‐known SUB1 gene. Pyramiding qSUB2 with the SUB1 gene locus is expected to further improve submergence tolerance in elite rice varieties.

Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment.

PurposeSpecific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping.MethodWe performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype.ResultsA suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis.ConclusionsThese results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI.Supplemental Material https://doi.org/10.23641/asha.13203218

QTL Analysis of Resistance to High-Intensity UV-B Irradiation in Soybean (Glycine max [L.] Merr.).

High-intensity ultraviolet-B (UV-B) irradiation is a complex abiotic stressor resulting in excessive light exposure, heat, and dehydration, thereby affecting crop yields. In the present study, we identified quantitative trait loci (QTLs) for resistance to high-intensity UV-B irradiation in soybean (Glycine max [L.]). We used a genotyping-by-sequencing approach using an F6 recombinant inbred line (RIL) population derived from a cross between Cheongja 3 (UV-B sensitive) and Buseok (UV-B resistant). We evaluated the degree of leaf damage by high-intensity UV-B radiation in the RIL population and identified four QTLs, UVBR12-1, 6-1, 10-1, and 14-1, for UV-B stress resistance, together explaining 20% of the observed phenotypic variation. The genomic regions containing UVBR12-1 and UVBR6-1 and their syntenic blocks included other known biotic and abiotic stress-related QTLs. The QTL with the highest logarithm of odds (LOD) score of 3.76 was UVBR12-1 on Chromosome 12, containing two genes encoding spectrin beta chain, brain (SPTBN, Glyma.12g088600) and bZIP transcription factor21/TGACG motif-binding 9 (bZIP TF21/TGA9, Glyma.12g088700). Their amino acid sequences did not differ between the mapping parents, but both genes were significantly upregulated by UV-B stress in Buseok but not in Cheongja 3. Among five genes in UVBR6-1 on Chromosome 6, Glyma.06g319700 (encoding a leucine-rich repeat family protein) had two nonsynonymous single nucleotide polymorphisms differentiating the parental lines. Our findings offer powerful genetic resources for efficient and precise breeding programs aimed at developing resistant soybean cultivars to multiple stresses. Furthermore, functional validation of the candidate genes will improve our understanding of UV-B stress defense mechanisms.

The Lr46 Gene Conditions Partial Adult‐ Plant Resistance to Stripe Rust, Stem Rust, and Powdery Mildew in Thatcher Wheat

ABSTRACTDisease resistance is a critical goal for many wheat (Triticum aestivum L.) improvement programs. Wheat cultivars are affected by multiple diseases including the rusts and powdery mildew. The F6 recombinant inbred lines (RILs) derived from ‘Thatcher’∗3/‘CI13227’ that had been previously characterized as having adult‐plant leaf rust resistance gene Lr46 were further tested for resistance to stripe rust, stem rust, and powdery mildew. In field plot tests, the RILs segregated for resistance to stripe rust, stem rust, and powdery mildew, with the highest logarithm of odds (LOD) peak at the sequence tagged site marker csLV46, which is closely linked to Lr46 on chromosome 1BL. Marker csLV46 had the highest LOD scores and R2 values for powdery mildew resistance, followed by stripe rust and leaf rust resistance. Tests for stem rust resistance had the lowest LOD scores. An additional quantitative trait locus (QTL) on chromosome 7AL for leaf rust resistance derived from CI13227 was detected in two of the three leaf rust tests. A QTL for stem rust resistance on chromosome 7AL derived from Thatcher was detected in two of the three stem rust tests.

Screening of candidate genes associated with constitutive aerenchyma formation in adventitious roots of the teosinte Zea nicaraguensis

Zea nicaraguensis (teosinte), a wild relative of maize (Zea mays ssp. mays), constitutively forms aerenchyma, which contributes to plant waterlogging tolerance, in the root cortex in drained soil, whereas maize (inbred line Mi29) does not. One with highest logarithm of odds (LOD) among quantitative trait loci (QTLs) that control constitutive aerenchyma formation in Z. nicaraguensis is Qaer1.05-6 on chromosome 1. Here, we attempted to identify genes in Qaer1.05-6 by comparing cDNA libraries from Mi29, Z. nicaraguensis and a hybrid (BC4F1 #62) carrying Qaer1.05-6. We first confirmed that constitutive aerenchyma formation was apparently observed in the order Z. nicaraguensis > BC4F1 #62 > Mi29. Contigs were assembled from cDNAs pooled from the three lines. We identified 1,868 contigs in the region on chromosome 1 that contained Qaer1.05-6. These contigs were screened for contigs that were predominantly composed of cDNAs from BC4F1 #62 and Z. nicaraguensis (no more than 10% of cDNAs from Mi29). Twenty-one such contigs were found and the genes they encoded were identified. In a real-time reverse transcription-polymerase chain reaction (RT- PCR) analysis, expression of six of these genes in BC4F1 #62 was at least double that in Mi29, making them candidates for genes associated with constitutive aerenchyma formation.

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 +/- 0.14). Mean LDL particle size and small LDL particle concentration (-0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration. Our results suggest a significant genetic contribution to multiple lipoprotein subclasses studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration.

Quantitative trait loci controlling resistance to cadmium rhizotoxicity in two recombinant inbred populations of Arabidopsis thaliana are partially shared by those for hydrogen peroxide resistance

To understand mechanisms of cadmium (Cd) tolerance variation associated with root elongation in Arabidopsis thaliana, quantitative trait loci (QTLs) and epistasis were analyzed using relative root length (RRL: % of the root length in +Cd to -Cd) as a tolerant index. Using the composite interval mapping method, three major QTLs (P < 0.05) were detected on chromosomes 2, 4 and 5 in the recombinant inbred population derived from a cross between Landsberg erecta (Ler-0) and Columbia (Col-4). The highest logarithm of odds (LOD) of 5.6 was detected with the QTL on chromosome 5 (QTL5), which is linked to the genetic marker CDPK9 and explained about 26% of the Cd tolerance variation. There was no significant difference in Cd-translocation ratio from roots to shoots between tolerant and sensitive recombinant inbreed lines (RILs), while greater accumulations of reactive oxygen species were observed in the roots of sensitive RILs. This suggested that accumulation of ROS would explain Cd tolerance variation of the Ler/Col RILs, which is mainly controlled by the QTL on chromosome 5. The QTL5 in Ler/Col population was also detected as one of the major QTLs controlling tolerances to hydrogen peroxide and to copper, which is another ROS generating rhizotoxic metal. The same chromosomal position was detected as a common major QTL for Cd and hydrogen peroxide tolerances in a different recombinant inbreed (RI) population derived from a cross of Col-gl1 and Kashmir (Kas-1). These data, along with a multitraits QTL analysis in both sets of RILs, suggest that peroxide damage depends on the genotype at a major Cd-tolerant locus on the upper part of chromosome 5.

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer's disease.

The aim of the study was to identify chromosomal regions that may harbor putative genetic variants influencing age at onset in familial late-onset Alzheimer's disease (LOAD). Data from a genome-wide scan that included genotyping of APOE were analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age at onset of 73.3 years multiply affected by LOAD. Two-point and multipoint analyses were conducted using variance component methods using 376 microsatellite markers with an average intermarker distance of 9.3 cM. Family-based test of association was also conducted for the same set of markers. Age at onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE-epsilon4 lowered the age at onset by 3 years. Several candidate loci were identified. Using linkage analysis strategy, the highest logarithm of odds (LOD) scores were obtained using a conservative definition of LOAD at 5q15 (LOD = 3.1), 17q25.1 (LOD = 2.94), 14q32.12 (LOD = 2.36), and 7q36.3 (LOD = 2.29) in a model that adjusted for APOE-epsilon4 and other covariates. Both linkage and family-based association identified 17p13 as a candidate region. Family-based association analysis showed markers at 12q13 (p = 0.00002), 13q33 (p = 0.00043), and 14q23 (p = 0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age at onset of late onset Alzheimer's disease. The novel loci at 5q15, 17q25.1, 13q33, and 17p13 and the previously reported loci at 7q36.3, 12q13, 14q23, and 14q32 need further investigation.

Genetic determinants of emotionality and stress response in AcB/BcA recombinant congenic mice and in silico evidence of convergence with cardiovascular candidate genes

Genomic loci bearing stress-related phenotypes were dissected in recombinant congenic strains (RCS) of mice with C57BL/6J (B6) and A/J progenitors. Adult male mice from 14 A/J and 22 B6 background lines were evaluated for emotional reactivity in open-field (OF) and elevated plus-maze tests. Core temperature was monitored by radio telemetry during immobilization and on standard as well as salt-enriched diets. In addition, urinary electrolytes were measured. Genome-wide linkage analysis of the parameters revealed over 20 significant quantitative trait loci (QTL). The highest logarithm of odds (LOD) scores were within the previously-reported OF emotionality locus on Chr 1 (LOD = 4.6), in the dopa decarboxylase region on Chr 11 for the plus-maze (LOD = 4.7), and within a novel region of calmodulin 1 on Chr 12 for Ca++ excretion after a 24-h salt load (LOD = 4.6). RCS stress QTL overlapped with several candidate loci for cardiovascular (CV) disease. In silico evidence of functional polymorphisms by comparative sequence analysis of progenitor strains assisted to ascertain this convergence. The anxious BcA70 strain showed down regulation of Atp1a2 gene expression in the heart (P < 0.001) and brain (P < 0.05) compared with its parental B6 strain, compatible with the enhanced emotionality described in knock out animals for this gene, also involved in the salt-sensitive component of hypertension. Functional polymorphisms in regulatory elements of candidate genes of the CV/inflammatory/immune systems support the hypothesis of genetically-altered environmental susceptibility in CV disease development.

Genome-Wide Linkage Analysis of Lipids in Nondiabetic Chinese and Japanese From the SAPPHIRe Family Study

Lipid levels are recognized as major risk factors for coronary heart disease (CHD). Discovery of major loci underlying quantitative lipid traits could help to elucidate the genetics of CHD. We performed a genome-wide search for quantitative trait loci linked to lipid phenotypes in 1538 Chinese subjects (509 families) and 625 Japanese subjects (204 families) not taking lipid-lowering medications from the Stanford-Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) study. The multipoint variance-components method was used to test for linkage between marker loci and each trait by maximum likelihood methods adjusted for effects of age, age(2), gender, body mass index (BMI), smoking, alcohol drinking, physical activity, and field center. The highest logarithm of odds (LOD) score detected was 3.22 for logarithmically transformed HDL-cholesterol on chromosome 12 at 113 cM in Chinese subjects. This score overlaps the positive findings for HDL reported in Mexican Americans (chromosome 12 at 96 cM). Although no strong evidence for linkage was found in Japanese subjects, some modest peaks (LOD score >==1.5) were found in several regions that have been reported in other published genome scans. For example, the Japanese SAPPHIRe peak for HDL (chromosome 1 at 167 cM; LOD = 1.54) was very close to the quantitative trait loci (QTL) for HDL reported in the scan of white American HyperGEN (chromosome 1 at 159.9 cM). Genome-wide scan for genes influencing lipid phenotypes was conducted and we found significant linkage of HDL to a locus on chromosome 12 in Chinese subjects and no linkage signal exceeding 1.68 was found in the Japanese subjects.

Linkage analysis of circulating levels of adiponectin in hispanic children

Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and proinflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VIVA LA FAMILIA Study by use of a systematic genome scan. The present study included extended families with at least one overweight child between 4 and 19 years old. Overweight was defined as body mass index (BMI) 95th percentile. Fasting blood was collected from 466 children from 127 families. Adiponectin was assayed by radioimmunoassay (RIA) technique in fasting serum. A genome-wide scan on circulating levels of adiponectin as a quantitative phenotype was conducted using the variance decomposition approach. The highest logarithm of odds (LOD) score (4.2) was found on chromosome 11q23.2-11q24.2, and a second significant signal (LOD score=3.0) was found on chromosome 8q12.1-8q21.3. In addition, a signal suggestive of linkage (LOD score=2.5) was found between 18q21.3 and 18q22.3. After adjustment for BMI-Z score, the LOD score on chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found on chromosome 3 (LOD score=2.1) and 10 (LOD score=2.5). Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this region for adiponectin levels. Our suggestive linkages on chromosomes 10 and 3 replicate results for adiponectin seen in other populations. The influence of loci on chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in the present study. Our genome scan in children has identified a novel QTL and replicated QTLs in chromosomal regions previously shown to be linked with obesity and type 2 diabetes (T2D)-related phenotypes in adults. The genetic contribution of loci to adiponectin levels may vary across different populations and age groups. The strong linkage signal on chromosome 11 is most likely underlain by a gene(s) that may contribute to the high susceptibility of these Hispanic children to obesity and T2D.

Linkage of Plasma Adiponectin Levels to 3q27 Explained by Association With Variation in the APM1 Gene

We performed a genome-wide linkage scan of plasma adiponectin levels in 569 nondiabetic participants in the Amish Family Diabetes Study. The highest logarithm of odds (LOD) score (2.13; P = 0.0009) occurred on chromosome 3q27 between markers D3S1602 and D3S1580, which flank APM1/ACDC, the adiponectin gene. The APM1 +2019 A/- insertion/deletion polymorphism in the 3' untranslated region (single nucleotide polymorphism [SNP] +2019; deletion allele frequency 0.30 in Amish) showed strong association with adiponectin levels in a dosage-dependent manner in a direction consistent with that reported in previous studies, with deletion heterozygosity increasing adiponectin levels by 1.3 +/- 0.5 microg/ml and deletion homozygosity increasing levels by 3.0 +/- 0.8 microg/ml (P < 0.0001). Two other SNPs, rs2241766 and rs1501299, showed moderate association. In a subset of 523 subjects genotyped for both SNP +2019 and rs2241766, including the APM1 SNP +2019 genotype as a covariate reduced the linkage signal at 3q27 by 1.26 LOD units (from 2.22 to 0.96) and including both SNPs reduced the signal by 1.51 LOD units (to 0.71). These findings, combined with a two-point LOD score of 2.35 for SNP +2019, provide evidence that variation in APM1 is responsible for linkage of adiponectin levels to 3q27 in the Old Order Amish.

Genetic susceptibility loci for essential hypertension and blood pressure on chromosome 17 in 147 Chinese pedigrees.

We scanned human chromosome 17 to verify previous studies on the chromosome as well as to explore possible new loci of essential hypertension in a Chinese Han population. A genomic scan of chromosome 17 with 15 microsatellite markers was conducted in a total of 757 individuals from 147 Chinese hypertension pedigrees. We used three softwares to analyse hypertension as a qualitative trait and blood pressure as quantitative phenotypes linkage analyses in the North group (406 individuals from 78 northern families), the South group (351 individuals from 69 southern families) and the combined group of the Chinese population separately. For qualitative trait, a 7-cM (centiMorgan) interval flanked by D17S831 (7 cM) and D17S938 (15 cM) showed suggestive linkage results (P < 0.00074) in the southern population by SAGE/SIBPAL2. For blood pressure (BP) quantitative phenotypes, the regions with lowest P values in SAGE and highest logarithm of odds (LOD) scores in SOLAR just overlapped this 7-cM interval in the South group for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), though these peaks did not yet reach to the suggestive linkage criteria (P = 0.00074, LOD score = 2.2). In the northern population, in a region around 75.0 cM (D17S787) a peak was found with non-parametric-linkage (NPL) score 1.82 for qualitative trait using GENEHUNTER. In the southern population of China, our results demonstrate that a 7-cM interval region flanked by D17S831 (7 cM) and D17S938 (15 cM) is suggestively linked with hypertension.

Altered mouse cholinephosphotransferase gene expression in kidneys of type 2 diabetic KK/TA mouse

It is generally considered that genetic factors may contribute to the susceptibility of type 2 diabetic nephropathy. The purpose of the present study is to identify molecules that contribute to the development and/or progression of this disease. Differential display was performed to isolate genes in the kidney using the KK/Ta mouse model of type 2 diabetes. The differential expression of 8 randomly chosen candidate genes (DN1–8) were verified by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis. DN1–3 (Zn-α2-glycoprotein, vascular endothelial growth factor receptor [VEGFR]-2, and lactate dehydrogenase [LDH]) were overexpressed and DN7–8 (peroxisome proliferator-activated receptor [PPAR]-interacting protein [PRIP], unknown) were underexpressed in the KK/Ta mouse kidney. DN4–6 (Ezrin, transcobalamin 2, aldo-ketoreductase) did not differ between KK/Ta and control (BALB/c) mice. DN8 only showed no significant sequence similarity to previously reported genes. Molecular cloning revealed that full-length DN8 shares 89% identity with human cholinephosphotransferase 1 ( hCHPT1), and we designated it as “putative” mouse cholinephosphotransferase 1 ( mCHPT1). The putative mCHPT1 gene was most closely mapped to the D10Mit94 locus with the highest logarithm of odds (lod) score. In situ hybridization revealed the levels of glomerular putative mCHPT1 in BALB/c mice tended to be slightly higher than those in KK/Ta mice. The altered renal mRNA expression of these genes may be involved in the development and/or progression of diabetic nephropathy.