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Biomedical subjects

Ya-Ping Zhang

Publications and source records attributed to Ya-Ping Zhang.

At least 37 records · Page 2Linked to original sources

Identification of genes differentially expressed in wild type and Purkinje cell degeneration mice.

Purkinje cell degeneration (pcd) mice are characterized by death of virtually all cerebellar Purkinje cells by postnatal day 30. In this study, we used DNA microarray analysis to investigate differences in gene expression between the brains of wild type and pcd mice on postnatal day 20, before the appearance of clear-cut phenotypic abnormalities. We identified 300 differentially expressed genes, most of which were involved in metabolic and physiological processes. Among the differentially expressed genes were several calcium binding proteins including calbindin-28k, paravalbumin, matrix gamma-carboxyglutamate protein and synaptotagamins 1 and 13, suggesting the involvement of abnormal Ca2+ signaling in the pcd phenotype.

Alleles↗

Evolutionary implications of multiple SINE insertions in an intronic region from diverse mammals.

An analysis of the nuclear beta-fibrinogen intron 7 locus from 30 taxa representing 12 placental orders of mammals reveals the enriched occurrences of short interspersed element (SINE) insertion events. Mammalian-wide interspersed repeats (MIRs) are present at orthologous sites of all examined species except those in the order Rodentia. The higher substitution rate in mouse and a rare MIR deletion from rat account for the absence of MIR in the rodents. A minimum of five lineage-specific SINE sequences are also found to have independently inserted into this intron in Carnivora, Artiodactyla and Lagomorpha. In the case of Carnivora, the unique amplification pattern of order-specific CAN SINE provides important evidence for the "pan-carnivore" hypothesis of this repeat element and reveals that the CAN SINE family may still be active today. Particularly interesting is the finding that all identified lineage-specific SINE elements show a strong tendency to insert within or in very close proximity to the preexisting MIRs for their efficient integrations, suggesting that the MIR element is a hot spot for successive insertions of other SINEs. The unexpected MIR excision as a result of a random deletion in the rat intron locus and the non-random site targeting detected by this study indicate that SINEs actually have a greater insertional flexibility and regional specificity than had previously been recognized. Implications for SINE sequence evolution upon and following integration, as well as the fascinating interactions between retroposons and the host genomes are discussed.

Animals↗

Mitochondrial diversity and phylogeographic structure of Chinese domestic goats.

China has numerous native domestic goat breeds, but so far there has been no extensive study on genetic diversity, population demographic history, and origin of Chinese goats. Here, we examined the genetic diversity and phylogeographic structure of Chinese domestic goats by determining a 481-bp fragment of the first hypervariable region of mitochondrial DNA (mtDNA) control region from 368 individuals representing 18 indigenous breeds. Phylogenetic analyses revealed that there were four mtDNA lineages (A-D) identified in Chinese goats, in which lineage A was predominant, lineage B was moderate, and lineages C and D were at low frequency. These results further support the multiple maternal origins of domestic goats. The pattern of genetic variation in goat mtDNA sequences indicated that the two larger lineages A and B had undergone population expansion events. In a combined analysis of previously reported sequences and our sequences belonging to lineage B, we detected two subclades, in which one was unique to eastern Asia and another was shared between eastern and southern Asia. A larger genetic variation in eastern Asia than southern Asia and the pattern of phylogeographic variation in lineage B suggest that at least one subclade of lineage B originated from eastern Asia. There was no significant geographical structuring in Chinese goat populations, which suggested that there existed strong gene flow among goat populations caused by extensive transportation of goats in history.

Animals↗

Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies.

An up-to-date view of the worldwide mitochondrial DNA (mtDNA) phylogeny together with an evaluation of the conservation of each site is a reliable tool for detecting errors in mtDNA studies and assessing the functional importance of alleged pathogenic mutations. However, most of the published studies on mitochondrial diseases make very little use of the phylogenetic knowledge that is currently available. This drawback has two inadvertent consequences: first, there is no sufficient a posteriori quality assessment of complete mtDNA sequencing efforts; and second, no feedback is provided for the general mtDNA database when apparently new mtDNA lineages are discovered. We demonstrate, by way of example, these issues by reanalysing three mtDNA sequencing attempts, two from Europe and another one from East Asia. To further validate our phylogenetic deductions, we completely sequenced two mtDNAs from healthy subjects that nearly match the mtDNAs of two patients, whose sequences gave problematic results.

Artifacts↗

Molecular phylogeny of Sinocyclocheilus (Cypriniformes: Cyprinidae) inferred from mitochondrial DNA sequences.

More than 10 species within the freshwater fish genus Sinoncyclocheilus adapt to caves and show different degrees of degeneration of eyes and pigmentation. Therefore, this genus can be useful for studying evolutionary developmental mechanisms, role of natural selection and adaptation in cave animals. To better understand these processes, it is indispensable to have background knowledge about phylogenetic relationships of surface and cave species within this genus. To investigate phylogenetic relationships among species within this genus, we determined nucleotide sequences of complete mitochondrial cytochrome b gene (1140 bp) and partial ND4 gene (1032 bp) of 31 recognized ingroup species and one outgroup species Barbodes laticeps. Phylogenetic trees were reconstructed using maximum parsimony, Bayesian, and maximum likelihood analyses. Our phylogenetic results showed that all species except for two surface species S. jii and S. macrolepis clustered as five major monophyletic clades (I, II, III, IV, and V) with strong supports. S. jii was the most basal species in all analyses, but the position of S. macrolepis was not resolved. The cave species were polyphyletic and occurred in these five major clades. Our results indicate that adaptation to cave environments has occurred multiple times during the evolutionary history of Sinocyclocheilus. The branching orders among the clades I, II, III, and IV were not resolved, and this might be due to early rapid radiation in Sinocyclocheilus. All species distributed in Yunnan except for S. rhinocerous and S. hyalinus formed a strongly supported monophyletic group (clade V), probably reflecting their common origins. This result suggested that the diversification of Sinocyclocheilus in Yunnan may correlate with the uplifting of Yunnan Plateau.

Adaptation, Physiological↗

Phylogenetic relationships of the macaques (Cercopithecidae: Macaca), inferred from mitochondrial DNA sequences.

To study the phylogenetic relationships of the macaques, five gene fragments were sequenced from 40 individuals of eight species: Macaca mulatta, M. cyclopis, M. fascicularis, M. arctoides, M. assamensis, M. thibetana, M. silenus, and M. leonina. In addition, sequences of M. sylvanus were obtained from Genbank. A baboon was used as the outgroup. The phylogenetic trees were constructed using maximum-parsimony and Bayesian methods. Because five gene fragments were from the mitochondrial genome and were inherited as a single entity without recombination, we combined the five genes into a single analysis. The parsimony bootstrap proportions we obtained were higher than those from earlier studies based on the combined mtDNA dataset. Excluding M. arctoides, our results are generally consistent with the classification of Delson (1980). Our phylogenetic analyses agree with earlier studies suggesting that the mitochondrial lineages of M. arctoides share a close evolutionary relationship with the mitochondrial lineages of the fascicularis group of macaques (and M. fascicularis, specifically). M. mulatta (with respect to M. cyclopis), M. assamensis assamensis (with respect to M. thibetana), and M. leonina (with respect to M. silenus) are paraphyletic based on our analysis of mitochondrial genes.

Animals↗

Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans.

The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-B2-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans.

Adult↗

Composition and evolution of the V2r vomeronasal receptor gene repertoire in mice and rats.

Pheromones are chemicals produced and detected by conspecifics to elicit social/sexual physiological and behavioral responses, and they are perceived primarily by the vomeronasal organ (VNO) in terrestrial vertebrates. Two large superfamilies of G protein-coupled receptors, V1rs and V2rs, have been identified as pheromone receptors in vomeronasal sensory neurons. Based on a computational analysis of the mouse and rat genome sequences, we report the first global draft of the V2r gene repertoire, composed of approximately 200 genes and pseudogenes. Rodent V2rs are subject to rapid gene births/deaths and accelerated amino acid substitutions, likely reflecting the species-specific nature of pheromones. Vertebrate V2rs appear to have originated twice prior to the emergence of the VNO in ancestral tetrapods, explaining seemingly inconsistent observations among different V2rs. The identification of the entire V2r repertoire opens the door to genomic-level studies of the structure, function, and evolution of this diverse group of sensory receptors.

Amino Acid Sequence↗

Phylogenetic studies of pantherine cats (Felidae) based on multiple genes, with novel application of nuclear beta-fibrinogen intron 7 to carnivores.

The pantherine lineage of the cat family Felidae (order: Carnivora) includes five big cats of genus Panthera and a great many midsized cats known worldwide. Presumably because of their recent and rapid radiation, the evolutionary relationship among pantherines remains ambiguous. We provide an independent assessment of the evolutionary history of pantherine lineage using two complete mitochondrial (mt) genes (ND2 and ND4) and the nuclear beta-fibrinogen intron 7 gene, whose utility in carnivoran phylogeny was first explored. The available four mt (ND5, cytb, 12S, and 16SrRNA) and two nuclear (IRBP and TTR) sequence loci were also combined to reconstruct phylogeny of 14 closely related cat species. Our analyses of combined mt data (six genes; approximately 3750 bp) and combined mt and nuclear data (nine genes; approximately 6500 bp) obtained identical tree topologies, which were well-resolved and strongly supported for almost all nodes. Monophyly of Panthera genus in pantherine lineage was confirmed and interspecific affinities within this genus revealed a novel branching pattern, with P. tigris diverging first in Panthera genus, followed by P. onca, P. leo, and last two sister species P. pardus and P. uncia. In addition, close association of Neofelis nebulosa to Panthera, the phylogenetic redefinition of Otocolobus manul within the domestic cat group, and the relatedness of Acinonyx jubatus and Puma concolor were all important findings in the resulting phylogenies. The potential utilities of nine different genes for phylogenetic resolution of closely related pantherine species were also evaluated, with special interest in that of the novel nuclear beta-fibrinogen intron 7.

Animals↗

Molecular phylogenetics and biogeography of Lepus in Eastern Asia based on mitochondrial DNA sequences.

In spite of several classification attempts among taxa of the genus Lepus, phylogenetic relationships still remain poorly understood. Here, we present molecular genetic evidence that may resolve some of the current incongruities in the phylogeny of the leporids. The complete mitochondrial cytb, 12S genes, and parts of ND4 and control region fragments were sequenced to examine phylogenetic relationships among Chinese hare taxa and other leporids throughout the World using maximum parsimony, maximum likelihood, and Bayesian phylogenetic reconstruction approaches. Using reconstructed phylogenies, we observed that the Chinese hare is not a single monophyletic group as originally thought. Instead, the data infers that the genus Lepus is monophyletic with three unique species groups: North American, Eurasian, and African. Ancestral area analysis indicated that ancestral Lepus arose in North America and then dispersed into Eurasia via the Bering Land Bridge eventually extending to Africa. Brooks Parsimony analysis showed that dispersal events followed by subsequent speciation have occurred in other geographic areas as well and resulted in the rapid radiation and speciation of Lepus. A Bayesian relaxed molecular clock approach based on the continuous autocorrelation of evolutionary rates along branches estimated the divergence time between the three major groups within Lepus. The genus appears to have arisen approximately 10.76 MYA (+/-0.86 MYA), with most speciation events occurring during the Pliocene epoch (5.65+/-1.15 MYA approximately 1.12 +/- 0.47 MYA).

Animals↗

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids.

The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree. Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.

Animals↗

[The genetic diversity of the second exon about SLA-DQB in some Chinese native pigs].

Polymorphism of the second exon about SLA-DQB genes in some Chinese native pigs was investigated employing PCR-SSCP analysis and DNA cloning sequencing. Combined with the sequences in GenBank, 73 new alleles were gained, among them function alleles of SLA-DQB were sixty-eight, five alleles of pseudogene (SLA-DXB) were gained. There were disequilibrium distribution of the alleles in all breeds, the same allele was shared by most breeds. C08 allele existed in 11 breeds of six groups and in the wild pigs of Yunnan and Sichuan province, and its frequency reached 55.10%. More than five sequences were found in each individual, suggesting duplication in these loci examined, there were three copies about SLA-DQB genes. The variable sites based on nucleotide and amino acids reached to eighty-one and forty-nine, respectively. The values of allelic diversity (H=0.889) and the nucleotide diversity (Pi=0.047) were revealed very high, from both values of H and Pi were higher in the beta pleated sheet region than those in alpha helix region in Chinese native pigs. In general, values of H and Pi in Huanan pigs and Xinan pigs were higher, vice versa in Tibet pigs. The genetic distance within group were showed the same order as comparison Pi values, hence we concluded the different rate of nucleotide substitution were positive correlated with the degree of nucleotide diversity in Chinese domestic groups. The genetic distances about SLA-DQB gene between groups were detected as follow: the great genetic distance were existed between the Jianghai and Huabei groups, and the smallest genetic distance were existed between the Huazhong and Gaoyuan groups.

Alleles↗

Bitter and sweet/umami taste receptors with differently evolutionary pathways.

In this study,we investigated the evolutionary pathways of bitter, sweet and umami receptors using bioinformatic and phylogenetic analyses. Our results showed that the distantly evolutionary relationship between bitter and sweet/umami receptors. Our results also showed that bitter and sweet/umami receptors have differently evolutionary pathways,suggesting that the different evolutionary pathways may resulte in the differences of these three receptors in function.

Amino Acid Sequence↗

[Genetic differentiation of domestic goose breeds in China].

The 1 042 bp control region of mitochondrial DNA from 84 geese of 15 domestic goose breeds was sequenced and genetic differentiation was analysed. Results showed that the interpopulation nucleotide divergence was highest (3.805% -4.067%) between Yili and the other 14 breeds. The average nucleotide diversity variation within different domestic breeds was 0 - 0.116%. Excluding the Yili, the interpopulation nucleotide divergence between Huoyan and the remaining breeds, was 0.211% - 0.272%, which was significantly higher than that between any other two breeds (0 -0.094%). During the formation of domestic breeds in China,there is an association between the genetic differentiation of domestic geese and their geographic distribution. The divergence time of Huoyan breed was relatively earlier and genetic drift may have been the main factor to affect the genetic differentiation of the Huoyan breed (Nm = 0.02 -0.54). On the other hand, gene flow is the main reason for the lack of a clear differentiation among the remaining 13 Chinese domestic geese breeds (Nm = 12.0 - 65.33).

Animals↗

[Sequence variation of TYR exon 1 and origin of pigs].

To investigate the origin and genetic diversity of domestic pigs, the porcine TYR exon 1 in 36 individuals from 12 Chinese indigenous breeds, three European breeds, eight Chinese wild boars and two Vietnamese wild boars was sequenced. Sequence analysis revealed six synonymous mutations, and all the sequences could be sorted into 4 haplotypes. Combining with the published sequences, we constructed a reduced median network (RM network), in which TYR*2 was a haplotype dominated by European domestic pigs and wild boars, plus only three chromosomes from Asian pigs. Most Asian domestic pigs and wild boars shared haplotype TYR*1, demonstrating that TYR*1 was an Asian specific haplotype. Meanwhile, some European domestic pigs and wild boars carried the haplotype TYR*1. TYR*3 and TYR*4 were two haplotypes with low frequencies, containing mainly Chinese indigenous pigs and Asian wild boars, plus some European domestic pigs. Independent domestication of pigs from Asia and Europe was supported by the pattern of RM network. The European commercial breeds had been suffered from introgression from Chinese pigs, and a few Chinese indigenous breeds and Japanese wild boars were also suffered from introgression from European pigs as well.

Animals↗

Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia.

To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA) haplogroups of India and determine the relationship between the Indian and western Eurasian mtDNA pools more precisely, a diverse subset of 75 macrohaplogroup N lineages was chosen for complete sequencing from a collection of >800 control-region sequences sampled across India. We identified five new autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously described only by first hypervariable segment (HVS-I) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup N, harbors at least as many deepest-branching lineages as the western Eurasian mtDNA pool. Moreover, the distribution of the earliest branches within haplogroups M, N, and R across Eurasia and Oceania provides additional evidence for a three-founder-mtDNA scenario and a single migration route out of Africa.

Base Sequence↗