Discovery of Digenic Mutation, KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing

Long QT syndrome(LQTS),which is caused by an ion channel–related gene mutation,is a malignant heart disease with a clinical course of a high incidence of ventricular fi brillation and sudden cardiac death in the young.Mutations in KCNH2(which encodes potassium voltage-gated channel subfamily H member 2)are responsible for LQTS in many patients.Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing.The c.916dupA mutation in JUP(which encodes junction plakoglobin)is also discovered.Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy.The double mutation in the proband may help explain his severe clinical manifestations,such as sudden cardiac death at an early age.Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line,while the mutation in JUP came from his maternal line.The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

Digenic heterozygous mutations in EYS/LRP5 in a Chinese family with retinitis pigmentosa

Dear Editor,I am Dr.Ji-Hong Wu,from the Department of Ophthalmology,Eye＆ENT Hospital of Fudan University,China.I write to present a case report of retinitis pigmentosa（RP）caused by novel digenic heterozygous mutations in a Chinese family.

Genetic analyses of Chinese patients with digenic oculocutaneous albinism

Background Oculocutaneous albinism （OCA） is a heterogeneous and autosomal recessive disorder in all populations worldwide. The mutational spectra of OCA are population-specific. Some OCA patients carry mutations from different OCA genes. In this study, we investigated the frequency of digenic mutations in Chinese OCA patients. Methods Genomic DNAs were extracted from the blood samples of 184 clinically diagnosed OCA patients and 120 unaffected subjects. The amplified DNA segments of the exons and exon-intron boundaries were screened for mutations of TYR, OCA2, TYRP1, SLC45A2, and HPS1 by direct sequencing. To exclude the previously unidentified alleles from polymorphisms, samples from 120 unaffected controls were sequenced for the same regions of variations. Results In all 184 patients, 134 had two pathologic mutations on one locus. Eleven cases had no apparent pathologic mutations in any of the genes studied. Among the remaining 39 patients who had only one pathologic mutation, five patients （2.7% in total） were found to carry the mutational alleles on a second locus in TYR, OCA2 or SLC45A2. Of the five digenic OCA patients, four patients were clinically diagnosed as OCA2 and one patient as OCAI. A previous unidentified allele p.G188D in SLC45A2 was identified, which was not present in the 120 unaffected controls. Conclusions The identification of the digenic OCA patients suggests the synergistic roles among TYR, OCA2 and SLC45A2 during melanin biosynthesis, which may cause OCA under digenic mutations. This information will be useful for gene diagnosis and genetic counseling of OCA in China.

QTL Analysis for Plant Height with Molecular Markers in Maize

Plant height has become one of important agronomic traits with the increase of planting density recently and the rapid developments of molecular markers have provided powerful tools to localize important agronomic QTL at the genomic level. The purposes of this investigation are to map plant height QTL with molecular markers and to analyze their genetic effects in maize. An F 2∶3 population from an elite combination (Zong3×87-1) was utilized for evaluating plant height in two locations, Wuhan and Xiangfan, with a randomized complete block design. The mapping population included 266 F 2∶3 family lines. A genetic linkage map, containing 150 SSR and 24 RFLP markers, was constructed, spanning a total of 2 531.6 cm with an average interval of 14.5 cm. Totally 10 QTL affecting plant height were mapped on six different chromosomes with the composite interval mapping. Seven of 10 QTL were detected in two locations. The contributions to phenotypic variations for the single QTL varied between 5.3 and 17.1%. Additive, partial dominance, dominance, and overdominance actions existed among all detected QTL affecting plant heights. A large number of digenic interactions for plant height were detected by two-way analyses of variance. 107 and 98 two-locus combinations were found to be significant at a 0.01 probability level in two locations respectively. 23 of them were simultaneously detected in both locations. They accounted for phenotypic variations of 4.511%. It was noticed that a locus, umc1122, had digenic interactive effects with other four different loci for plant height, which distributed on three chromosomes. A few of plant height QTL was involved in significant digenic interactions, but most significant interactions occurred between markers that are not adjacent to mapped QTL. These results demonstrated that epistatic interactions might play an equal importance role as the single-locus effects in determining plant height of maize.

Genetic Components of Heterosis for Seedling Traits in an Elite Rice Hybrid Analyzed Using an Immortalized F2 Population

Utilization of heterosis has greatly contributed to rice productivity in China and many Asian countries. Superior hybrids usually show heterosis at two stages： canopy development at vegetative stage and panicle development at reproductive stage resulting in heterosis in yield. Although the genetic basis of heterosis in rice has been extensively investigated, all the previous studies focused on yield traits at maturity stage. In this study, we analyzed the genetic basis of heterosis at seedling stage making use of an ＂immortalized F2＂ population composed of 105 hybrids produced by intercrossing recombinant inbred lines （RILs） from a cross between Zhenshan 97 and Minghui 63, the parents of Shanyou 63, which is an elite hybrid widely grown in China. Eight seedling traits, seedling height, tiller number, leaf number, root number, maximum root length, root dry weight, shoot dry weight and total dry weight, were investigated using hydroponic culture. We analyzed single-locus and digenic genetic effects at the whole genome level using an ultrahigh-density SNP bin map obtained by population re-sequencing. The analysis revealed large numbers of heterotic effects for seedling traits including dominance, over- dominance and digenic dominance （epistasis） in both positive and negative directions. Overdominance effects were prevalent for all the traits, and digenic dominance effects also accounted for a large portion of the genetic effects. The results suggested that cumulative small advantages of the single-locus effects and two-locus interactions, most of which could not be detected statistically, could explain the genetic basis of seedling heterosis of the F1 hybrid.