Genetic variation in South Indian castes: evidence from Y-chromosome, mitochondrial, and autosomal polymorphisms.

BACKGROUND: Major population movements, social structure, and caste endogamy have influenced the genetic structure of Indian populations. An understanding of these influences is increasingly important as gene mapping and case-control studies are initiated in South Indian populations. RESULTS: We report new data on 155 individuals from four Tamil caste populations of South India and perform comparative analyses with caste populations from the neighboring state of Andhra Pradesh. Genetic differentiation among Tamil castes is low (RST = 0.96% for 45 autosomal short tandem repeat (STR) markers), reflecting a largely common origin. Nonetheless, caste- and continent-specific patterns are evident. For 32 lineage-defining Y-chromosome SNPs, Tamil castes show higher affinity to Europeans than to eastern Asians, and genetic distance estimates to the Europeans are ordered by caste rank. For 32 lineage-defining mitochondrial SNPs and hypervariable sequence (HVS) 1, Tamil castes have higher affinity to eastern Asians than to Europeans. For 45 autosomal STRs, upper and middle rank castes show higher affinity to Europeans than do lower rank castes from either Tamil Nadu or Andhra Pradesh. Local between-caste variation (Tamil Nadu RST = 0.96%, Andhra Pradesh RST = 0.77%) exceeds the estimate of variation between these geographically separated groups (RST = 0.12%). Low, but statistically significant, correlations between caste rank distance and genetic distance are demonstrated for Tamil castes using Y-chromosome, mtDNA, and autosomal data. CONCLUSION: Genetic data from Y-chromosome, mtDNA, and autosomal STRs are in accord with historical accounts of northwest to southeast population movements in India. The influence of ancient and historical population movements and caste social structure can be detected and replicated in South Indian caste populations from two different geographic regions.

The isolation of arboviruses including a new flavivirus and a new Bunyavirus from Ixodes (Ceratixodes) uriae (Ixodoidea: Ixodidae) collected at Macquarie Island, Australia, 1975-1979.

Pools of ticks, Ixodes (Ceratixodes) uriae collected between 1975 and 1979 at Macquarie Island, yielded 33 strains of at least 4 different viruses: Nugget virus (Kemerovo group), 1 strain; Taggert virus (Sakhalin group) 9 strains; a previously undescribed flavivirus, related to Central European Tickborne encephalitis virus, for which the name "Gadgets Gully" is proposed, 9 strains; a virus serologically related to the Uukuniemi serogroup, family Bunyaviridae, for which the name "Precarious Point" is proposed, 10 strains. Three isolates were mixtures of Nugget and Gadgets Gully viruses; the remaining virus strain remains unidentified.

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway.

To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by >or=1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (P

Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia.

Several lines of evidence have implicated the catechol-O-methyltransferase (COMT) gene as a candidate for schizophrenia (SZ) susceptibility, not only because it encodes a key dopamine catabolic enzyme but also because it maps to the velocardiofacial syndrome region of chromosome 22q11 which has long been associated with SZ predisposition. The interest in COMT as a candidate SZ risk factor has led to numerous case-control and family-based studies, with the majority placing emphasis on examining a functional Val/Met polymorphism within this enzyme. Unfortunately, these studies have continually produced conflicting results. To assess the genetic contribution of other COMT variants to SZ susceptibility, we investigated three single-nucleotide polymorphisms (SNPs) (rs737865, rs4633, rs165599) in addition to the Val/Met variant (rs4680) in a highly selected sample of Australian Caucasian families containing 107 patients with SZ. The Val/Met and rs4633 variants showed nominally significant associations with SZ (P<0.05), although neither of the individual SNPs remained significant after adjusting for multiple testing (most significant P=0.1174). However, haplotype analyses showed strong evidence of an association; the most significant being the three-marker haplotype rs737865-rs4680-rs165599 (global P=0.0022), which spans more than 26 kb. Importantly, conditional analyses indicated the presence of two separate and interacting effects within this haplotype, irrespective of gender. In addition, our results indicate the Val/Met polymorphism is not disease-causing and is simply in strong linkage disequilibrium with a causative effect, which interacts with another as yet unidentified variant approximately 20 kb away. These results may help explain the inconsistent results reported on the Val/Met polymorphism and have important implications for future investigations into the role of COMT in SZ susceptibility.

Murray Valley encephalitis in Australia, 1974: antibody response in cases and community.

Fifty-three patients accepted on clinical grounds as cases of Murray Valley encephalitis (MVE) in Australia in 1974 were examined for antibody to MVE virus. Only one (who died early in the disease and whose diagnosis was confirmed by virus isolation) did not develop antibody; 13 patients showed stationary or single convalescent titres not diagnostic of recent infection, but other evidence that infection was recent was obtained in eight; 39 showed significant rise or fall in titre confirming recent infection. Haemagglutination-inhibition (HI) was more effective in establishing a diagnosis than complement-fixation (CF) although both tests were of value. Patients varied widely in timing and magnitude of rise and fall of titre. Two showed late rises in antibody titre which raises the possibility of recrudescent persisting infection. CF titres were enhanced in some sera by increase in the number of units of antigen used and by inactivation at 56 degrees C rather than 60 degrees C. Five patients with clinically-acceptable diagnoses of MVE (and one with minor illness) showed higher HI titres to Kunjin than to MVE virus. The results in several cases suggest that Kunjin virus was the infecting agent. In others it is possible that MVE infection had occurred in patients with pre-existing Kunjin antibody. HI reactivity to MVE virus was found in IgM fractions of sera taken for at least 40 days and in some cases for over 100 days after onset of symptoms. IgM fractions gave similar titres to MVE and Alfuy virus but clearly distinguished MVE-Alfuy and Kunjin viruses. HI antibody to MVE virus was found in about 10% of sera from family contacts or neighbours of patients with encephalitis, and in a similar proportion of patients in Victoria with various febrile illnesses not accepted as MVE. One patient with minor illness had antibody response to Kunjin virus. 2589 sera from pathology laboratories in towns in the Murray Valley gave additional evidence of community immunity to flaviviruses and suggested some increase in the proportion reactive between January and May 1974. HI and plaque reduction tests on these sera also gave evidence of antibody to Kunjin virus in the Murray Valley.

Treatment of intestinal parasites in Australian aboriginal children.

Five to nine-year-old Aboriginal children on Mitchell River Community maintained a satisfactory growth rate in the presence of multiple infections with intestinal parasites. Intensive treatment was successful in eliminating Giardia lamblia, Entamoeba histolytica, and Strongyloides stercoralis infections, but reinfection with G. lamblia was rapid. Treatment failed to produce any growth spurt in the group. This may have been due to the rapidity of reinfection, but raises the question of whether intestinal parasites contribute significantly to growth retardation or whether growth retarded children have an immune deficit rendering them more susceptible to parasitic infections.

Murray Valley encephalitis virus infection in mosquitoes and domestic fowls in Queensland, 1974.

Field studies during an epidemic of Murray Valley encephalitis (MVE) led to the isolation of MVE virus from a pool of mosquitoes (Culex annulirostris) and a sentinel chicken from Charleville, south-west Queensland. A high proportion of domestic fowls at Charleville had antibody to MVE virus at the beginning of February 1974, in advance of the first case recognized in Queensland and allowing early warning from health authorities. A survey of antibody in domestic fowls in mid-1974 suggested widespread activity of MVE virus in western and east-central Queensland. Virus isolation and serological studies showed activity in south-west Queensland of three other viruses known to infect man, Ross River, Sindbis and Kunjin viruses.

Antibody to togaviruses in the Northern Territory and adjoining areas of Australia.

Antibody to flaviviruses Murray Valley encephalitis (MVE) and Kunjin and to alphaviruses Ross River and Sindbis were found in many Aboriginal children and adults bled in central Australia in 1974 after several cases of MVE occurred there as part of a widespread epidemic. Antibody was also detected in sera taken in the period 1968 to 1973, but in a much lower proportion, suggesting both that the 1974 epidemic had caused frequent sub-clinical infection and that infection had occurred in the arid centre of Australia outside years of known togavirus activity. Evidence of frequent togavirus infection was found in sera from various species from monsoonal northern areas of Northern Territory and Western Australia, compatible with previous suggestions that togaviruses are enzootic or frequently epizootic in those areas.

Isolation of virus strains from mosquitoes collected in Queensland, 1972-1976.

171,348 mosquitoes and 4,353 other arthropods collected at three centres in Queensland in 1972-1976 yielded 151 strains of 18 viruses. Culex annulirostris was the major source of virus isolation but 42 strains from Aedes normanensis indicate it to be a vector of importance. Ross River and Kokobera viruses were isolated at Kowanyama in the dry season, a finding of interest as being compatible with year-round survival in vector-vertebrate cycles. Culex fatigans has in part replaced Culex annulirostris in peridomestic breeding sites at Kowanyama; the infrequency of virus isolation from it suggests that this replacement may lower arbovirus infection rates. Twelve strains were identified as viruses antigenically distinct from any previously isolated in Australia or New Guinea: Ch16129, showed by the International Reference Centre for Arboviruses to be a previously undescribed member of the Simbu Group (Facey's Paddock virus), Ch16313 (Murweh), Ch19520 (Parker's Farm) and Ch19546 (little Sussex). The remaining strains were identified as viruses previously known in Australia, but included many new host or geographical records.

Isolation of Sindbis (alphavirus) and Leanyer viruses from mosquitoes collected in the Northern Territory of Australia, 1974.

Mosquitoes collected near Darwin, Northern Territory, in 1974 yielded two virus strains. One was identified as Sindbis virus, not previously isolated from the Northern Territory. The other is antigenically distinct from viruses previously isolated from arthropods in Australia, and the name "Leanyer" is proposed for it. Its properties suggest that it may be a togavirus serologically unrelated to available alphaviruses and flaviviruses.

Peaton virus: a new Simbu group arbovirus isolated from cattle and Culicoides brevitarsis in Australia.

A new member of the Simbu group of arboviruses, for which the name Peaton virus is proposed, has been isolated from midges and cattle in Australia. Nine isolates were obtained from 101 pools of the biting midge Culicoides brevitarsis collected at Peachester, Qld, (26.51 degrees S., 152.53 degrees E.) between 30 November and 8 December 1976. Three isolations of the same virus were made from the blood of sentinel cattle collected at Grafton and Tamworth, N.S.W., on 20 January and 13 April 1977, respectively. Peaton virus was shown to be a member of the Simbu group of arboviruses by complement-fixation tests using antisera prepared against Australian strains of Akabane and Aino viruses. It was readily distinguishable from these viruses in cross-neutralization tests in tissue cultures and mice. A serological survey of sentinel cattle showed that neutralizing antibody was detectable only in cattle within the recorded limits of the suspected vector C. brevitarsis. Neutralizing antibody in blood serum was detected in 22 of 157 sheep, 21 of 137 horses, 7 of 18 buffaloes, 7 of 20 goats and 3 of 62 pigs, but not in 22 camels, 34 dogs, 3 cats, 76 human beings, 240 marsupials, 19 reptiles or 31 wild birds. The pathogenecity of Peaton virus has yet to be determined. The Yale Arbovirus Research Unit and the Center for Disease Control, Fort Collins, U.S.A., found that Peaton virus was distinguishable from all other Simbu group viruses and thus is a new virus.

Isolation of arboviruses from insects collected at Beatrice Hill, Northern Territory of Australia, 1974-1976.

Between October 1974 and May 1976, 57 596 mosquitoes, 169 957 Culicoides, 5923 Lasiohelea and 1043 phlebotomines were collected for virus isolation at Beatrice Hill (lat. 12 degrees 39'S.,long. 131 degrees 20'E.) in the Northern Territory of Australia. A total of 94 viruses belonging to 22 different serological groupings was isolated. The following species of insect yielded viruses which were identified and those viruses marked with an asterisk represent a new record of insect host: Culex annulirostris: Ross River, Kokobera, Barmah Forest, Corriparta, Eubenangee*, Wongorr; Anopheles amictus: Mapputta*; An bancroftii: bovine ephemeral fever*; An farauti: Eubenangee*; An annulipes: Mapputta; Culicoides marksi: Barmah Forest*, Belmont, Eubenangee*, Wallal, Warrego, Leanyer*, Parker's Farm*, Humpty Doo*; C. peregrinus: Beatrice Hill*; C. oxystoma: Bunyip Creek*, Marrakai*; C. pallidothorax: Wongorr*; C. histrio: Thimiri*; Lasiohelea spp.: Humpty Doo*. Pools of mixed species of Culicoides yielded bluetongue, Belmont, CSIRO Village, Warrego and Facey's Paddock viruses. Filter-passing agents not yet identified, were isolated from Cx annulirostris and An bancroftii. As well as providing new locality records for all but one of the 22 viruses isolated, the study yielded five new viruses (bluetongue serotype 20, CSIRO Village, Marrakai, Beatrice Hill and Humpty Doo viruses) and a new record for Thimiri virus which had not been recorded previously in Australia nor had it been isolated from an arthropod. Nine of the viruses isolated occur in more than one family of Diptera.