HUMAN MITOCHONDRIAL tRNA MUTATIONS IN MATERNALLY INHERITED DEAFNESS

Mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

Tolerance of Maize(Zea maysL.)to hlorsulfuron

Fourteen inbreds of maize were tested for the tolerance to chlorsulfuron with the method of seedling water culter.Significant difference existed in the tolerance of different type maize when tested with 1 and 2 μg/kg of chlorsulfuron.The tolerance in different type maize wa dent>flint>sugar>midiem>super sugarpop.The tolerance of different inbred maize was negative correlated with the concentration concentration of chorsulfuron.The tolerance of hybrids might have some relation with their parent lines because in this test the hybrids response to chlorsulfuron showed significant positive correlation with that of tits female parent which suggented some maternal in inheritance and was not controlled by nuclear.It was possible that tolerance of maize to chlorsulfuron was cytoplasm inheritance.

Development of organelle single nucleotide polymorphism (SNP) markers and their application for the identification of cytoplasmic inheritance patterns in Pyropia yezoensis (Bangiales,Rhodophyta)

The genus Pyropia contains several important cultivated species.Genetic research in nori species has mainly focused on the cell nucleus,with few studies on organelles(chloroplast and mitochondria).Due to the high copy numbers of organelles in cells,which influence the development and traits of algae,it is necessary to study their genetic mechanism.In this study,the marine red alga Pyropia yezoensis,an important economic macroalga,was selected as the study object.To investigate organelle(chloroplast and mitochondria)inheritance in P.yezoensis,the wild type RZ(maternal strain)was crossed with the red mutant HT(paternal strain)and 30 color-sectors from 11 F1 gametophytic blades were examined.The complete chloroplast and mitochondrial genomes of the red mutant(HT)were assembled for the first time.One reliable and stable single nucleotide polymorphism(SNP)loci filtrated by bioinformatics analysis was used as a molecular marker for chloroplast and mitochondrial DNA,respectively,in subsequent experiments.PCR amplification and sequence analysis showed that the haplotypes of color-sectors detected were consistent with those of the maternal parent,confirming that both chloroplast and mitochondrial genomes were inherited maternally in P.yezoensis.The inheritance pattern of organelles in P.yezoensis can be used to guide the hybridization and breeding of nori.Additionally,the organelle SNP markers developed in this study can be applied in subsequent genetic research.

The chloroplast genome comparative characteristic of artificial breeding tree,a case about Broussonetia kazinoki×Broussonetia papyrifera

Broussonetia kazinoki×Broussonetia papyrifera(ZJGS)is a hybrid species in Moraceae family,which has a very complicated hybrid origin.The excellent characteristics of fast growth,strong soil and water conservation ability,high leaf protein content and stem fiber content in ZJGS make it both ecological benefits in the mining area and economically valuable.This study aims to further understand ZJGS and other Moraceae taxa through the ZJGS chloroplast(cp)genome structure and the comparison with 12 closely related Moraceae species.Among the 13 Moraceae species,the cp genome length of seven Broussonetia species(ranges from 160,239 bp to 162,594 bp)is larger than that of six Morus species(ranges from 158,459 bp to 159,265 bp).Among the 77 shared protein-coding genes(PCGs)in Moraceae species,the obvious positive selection of Ka/Ks ratios acted on petD and rpl16 genes of B.kazinoki and B.papyrifera,respectively.Phylogenetic analysis based on shared PCGs from 28 species shows that ZJGS is closely related to maternal B.kazinoki.These findings provide data support for the origin of ZJGS hybridization and provide genomic resources for future ZJGS resource development and molecular breeding.

Mitochondrial hepatopathy: Respiratory chain disorders- ‘breathing in and out of the liver’

Mitochondria,the powerhouse of a cell,are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond.Evolution supports a prokaryotic descent,and,unsurprisingly,the organelle is worthy of being labeled an organism in itself.Since highly metabolically active organs require a continuous feed of energy,any dysfunction in the structure and function of mitochondria can have variable impact,with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition.Though categorized a hepatopathy,mitochondrial respiratory chain defects are not limited to the liver in time and space.The liver involvement is also variable in clinical presentation as well as in age of onset,from acute liver failure,cholestasis,or chronic liver disease.Other organs like eye,muscle,central and peripheral nervous system,gastrointestinal tract,hematological,endocrine,and renal systems are also variably involved.Diagnosis hinges on recognition of subtle clinical clues,screening metabolic investigations,evaluation of the extrahepatic involvement,and role of genetics and tissue diagnosis.Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation.This review lists and discusses the burden of mitochondrial respiratory chain defects,including various settings when to suspect,their evolution with time,including certain specific disorders,their tiered evaluation with diagnostic algorithms,management dilemmas,role of liver transplantation,and the future research tools.

Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans

Little is known about the inheritance of very low heteroplasmy mitochondria DNA （mtDNA） variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, cor- resnondin to abottleneck of about 200 mtDNA.

Sperm Mitochondria in Reproduction:Good or Bad and Where Do They Go?

The mitochondrion is the major energy provider to power sperm motility. In mammals, aside from the nuclear genome, mitochondrial DNA （mtDNA） also contributes to oxidative phosphorylation to impact production of ATP by coding 13 polypeptides. However, the role of sperm mitochondria in fertilization and its final fate after fertilization are still controversial. The viewpoints that sperm bearing more mtDNA will have a better fertilizing capability and that sperm mtDNA is actively eliminated during early embryogenesis are widely accepted. However, this may be not true for several mammalian species, including mice and humans. Here, we review the sperm mitochondria and their mtDNA in sperm functions, and the mechanisms of maternal mitochondrial inheritance in mammals.

Role of Heteroplasmic Mutations in the Mitochondrial Genome and the ID4 Gene Promoter Methylation Region in the Pathogenesis of Chronic Aplastic Anemia in Patients Suffering from Kidney Yin Deficiency

Objective： To analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia （CAA） suffering from Kidney （Shen） yin deficiency or Kidney yang deficiency. Methods： Bone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency （20 cases）. Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction （PCR）, and PCR products were used for sequencing and analysis. Results： Higher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency （positive rate, 60%） and Kidney yang deficiency （positive rate, 55%）. Conclusions： These data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CA,＆,. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.

Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism(IHH)and an oligogenic etiology has been suggested.However,the associated genes may account for only approximately 50%cases.In addition,a genomic systematic pedigree analysis is still lacking.Here,we conducted whole exome sequencing(WES)on 18 unrelated men affected by IHH and their corresponding parents.Notably,one reported and 10 novel variants in eight known IHH causative genes(AXL,CCDC141,CHD7,DMXL2,FGFR1,PNPLA6,POLR3A,and PR0KR2),nine variants in nine recently reported candidate genes(DCAF17,DCC,EGF,IGSF10,NOTCH1,PDE3A,RELN,SLIT2,and TRAPPC9),and four variants in four novel candidate genes for IHH(CCDC88C,CDON,GADL1,and SPRED3)were identified in 77.8%(14/18)of IHH cases.Among them,eight(8/18,44.4%)cases carried more than one variant in IHH-related genes,supporting the oligogenic model.Interestingly,we found that those variants tended to be maternally inherited(maternal with n=17 vs paternal with n=7;P=0.028).Our further retrospective investigation of published reports replicated the maternal bias(maternal with n=46 i^s paternal with n=28;P=0.024).Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.