QTLs for malting flavour component associated with pre-harvest sprouting susceptibility in barley (Hordeum vulgare L.)

Lipoxygenase (LOX) is a key factor affecting quality of beer in terms of foam stability and flavour. Low LOX content is a desirable trait for malting quality. A doubled haploid (DH) population was made from a cross of Australian malting barley Stirling and Canadian malting barley Harrington and mapped with 513 molecular markers. The 120 DH lines with their parents were planted in field trials and the harvested grains were micro-malted for analysis of LOX content in two consecutive years. LOX content was controlled by both genetic effects and environment conditions. Three QTLs were consistently detected. One QTL flanked by the markers E6216 and SCssr03907 at the telomere region of chromosome 5HL contributed 39% of genetic variation in LOX content. The second QTL close to the centromere region of chromosome 5H accounted for 17% of genetic variation. A minor QTL on chromosome 2H explained 6% of genetic variation but was significant in both years. The Australian variety Stirling contributed to higher LOX content for the three QTLs. The two QTLs mapped at chromosome 5H for LOX content coincided with the QTLs for seed dormancy/pre-harvest sprouting from the same population. The pre-harvest sprouting susceptible alleles were associated with low LOX content, which indicated that the low LOX QTL from the Canadian malting barleys are only useful in the barley growing areas where the pre-harvest sprouting risk is low. New genetic sources for low LOX should be exploited in different germplasm with different mechanisms

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

Seed dormancy in barley is dictated by genetics, environments and their interactions

The transition from dormancy to germination is crucial for malt barley in the malt house. Seed dormancy is a quantitative trait and the depths of dormancy controlled by environment/genetics remain unclear. Quantitative trait locus (QTL) analysis was conducted to evaluate the number, location and phenotypic variation explained by QTLs from data collected from different years, sites and germination conditions in the Stirling × Harrington population. QTLs on 4H, 5H and 6H could explain 25, 81 and 12 % of phenotypic variations, respectively. Consistent QTLs were detected on 5HL and other QTLs were subjected to growth or germination conditions. Germination tests under light detected more QTLs than in the dark. The QTL at 5HL were more important for seed dormancy under the Mediterranean environment and evidence showed at least two genes controlling seed dormancy at 5HL

NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak

A decrease in renal phosphate reabsorption with mild hypophosphatemia (phosphate leak) is found in some hypercalciuric stone-formers. The NPT2a gene encodes a sodium-phosphate cotransporter, located in the proximal tubule, responsible for reclaiming most of the filtered phosphate load in a rate-limiting manner. To determine whether genetic variation of the NPT2a gene is associated with phosphate leak and hypercalciuria in a cohort of 98 pedigrees with multiple hypercalciuric stone-formers, we sequenced the entire cDNA coding region of 28 probands, whose tubular reabsorption of phosphate normalized for the glomerular filtration rate (TmP/GFR) was 0.7 mmol/l or lower. We performed genotype/phenotype correlations for each genetic variant in the entire cohort and expressed NPT2a variant RNAs in Xenopus laevis oocytes to test for cotransporter functionality. We identified several variants in the coding region including an in-frame 21 bp deletion truncating the N-terminal cytoplasmic tail of the protein (91del7), as well as other single-nucleotide polymorphisms that were non-synonymous (A133V and H568Y) or synonymous. Levels of TmP/GFR and urine calcium excretion were similar in heterozygote carriers of NPT2a variants compared to the wild-type (wt) homozygotes. The transport activity of the H568Y mutants was identical to the wt, whereas the N-terminal-truncated version and the 91del7 and A133V mutants presented minor kinetic changes and a reduction in the expression level. Although genetic variants of NPT2a are not rare, they do not seem to be associated with clinically significant renal phosphate or calcium handling anomalies in a large cohort of hypercalciuric stone-forming pedigrees

Seed dormancy in barley: identifying superior genotypes through incorporating epistatic interactions

A genetic linkage map of barley with 128 molecular markers was constructed using a doubled haploid (DH) mapping population derived from a cross between barley (Hordeum vulgare) cvv. Stirling and Harrington. Quantitative trait loci controlling seed dormancy were characterised in the population. A major quantitative trait locus (QTL) controlling seed dormancy and accounting for over half the phenotypic variation (52.17%) was identified on the distal end of the long arm of chromosome 5H. Minor QTLs were also detected near the centromeric region of 5H and on chromosomes 1H and 3H. These minor QTLs with additive effects accounted for 7.52% of the phenotypic variance measured. Examination of epistatic interactions further detected additional minor QTLs near the centromere of 2H and on the long arm and short arms of 4H. Combinations of parental alleles at the QTL locations in predictive analyses indicated dramatic differences in germination. These results emphasise the potential differences in dormancy that can be achieved through the use of specific gene combinations and highlights the importance of minor genes and the epistatic interactions that occur between them. This study found that the combination of Stirling alleles at the two QTL locations on the 5H chromosome and Harrington alleles at the 1H and 3H QTL locations significantly produced the greatest dormancy. Uncovering gene complexes controlling the trait may enable breeders to produce superior genotypes with the desirable allele combinations necessary for manipulating seed dormancy in barley