Role of the thymus in the immune response to sheep erythrocytes in the lizard Calotes versicolor

The role of the thymus in antibody response to sheep erythrocytes (SRBC) was investigated in the lizard,Calotes versicolor, by utilizing the experimental models of adult thymectomy and anti-thymocyte serum (ATS) treatment. When thymectomized lizards were treated with high dose regimen of ATS, plaque-forming cell (PFC) response to SRBC was abrogated; however, this response was not altered by the low dose. A definite recovery of anti-SRBC response after ATS treatment occurred in the presence of the thymus. On the other hand the PFC response to SRBC was enhanced one month after adult thymectomy and after low dose ATS treatment. Both low and high doses of normal rabbit serum suppressed the immune response to SRBC and it is suggested that this suppression might be due to antigenic competition. These results indicate that (i) anti-SRBC response is thymus dependent and (ii) there are two kinds of thymus derived cells: one 'helper' collaborating in anti-SRBC response and another 'regulator' governing the magnitude of the response which is involved in antigenic competition. The phylogenetic status on the dual role of the thymus in immune functions has been discussed

The Genographic Project Public Participation Mitochondrial DNA Database

The Genographic Project is studying the genetic signatures of ancient human migrations and creating an open-source research database. It allows members of the public to participate in a real-time anthropological genetics study by submitting personal samples for analysis and donating the genetic results to the database. We report our experience from the first 18 months of public participation in the Genographic Project, during which we have created the largest standardized human mitochondrial DNA (mtDNA) database ever collected, comprising 78,590 genotypes. Here, we detail our genotyping and quality assurance protocols including direct sequencing of the mtDNA HVS-I, genotyping of 22 coding-region SNPs, and a series of computational quality checks based on phylogenetic principles. This database is very informative with respect to mtDNA phylogeny and mutational dynamics, and its size allows us to develop a nearest neighbor–based methodology for mtDNA haplogroup prediction based on HVS-I motifs that is superior to classic rule-based approaches. We make available to the scientific community and general public two new resources: a periodically updated database comprising all data donated by participants, and the nearest neighbor haplogroup prediction tool

From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes

Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users. Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling). Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources

The GenoChip: A New Tool for Genetic Anthropology

The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. TheGenoChip includes ancestry informativemarkers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all knownY-chromosome andmtDNAhaplogroups. The chip was carefully vetted to avoid inclusion ofmedically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highestmean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPswithout any known health,medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics

Geographic population structure analysis of worldwide human populations infers their biogeographical origins

The search for a method that utilizes biological information to predict humans’ place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an accuracy of 700 km in Europe, they were inaccurate elsewhere. Here we describe the Geographic Population Structure (GPS) algorithm and demonstrate its accuracy with three data sets using 40,000–130,000 SNPs. GPS placed 83% of worldwide individuals in their country of origin. Applied to over 200 Sardinians villagers, GPS placed a quarter of them in their villages and most of the rest within 50 km of their villages. GPS’s accuracy and power to infer the biogeography of worldwide individuals down to their country or, in some cases, village, of origin, underscores the promise of admixture-based methods for biogeography and has ramifications for genetic ancestry testing

Neolithic Mitochondrial Haplogroup H Genomes and the Genetic Origins of Europeans

Haplogroup H dominates present-day Western European mitochondrial DNA variability (\u3e40%), yet was less common (~19%) among Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete haplogroup H mitochondrial genomes from ancient human remains. We then compare this ‘real-time’ genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of haplogroup H were largely established by the Mid Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated haplogroup H genomes allow us to reconstruct the recent evolutionary history of haplogroup H and reveal a mutation rate 45% higher than current estimates for human mitochondria

Population differentiation of Southern Indian male lineages correlates with agricultural expansions predating the caste system

Christina J. Adler, Alan Cooper, Clio S.I. Der Sarkissian and Wolfgang Haak are contributors to the Genographic ConsortiumPrevious studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed, <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna(caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.GaneshPrasad ArunKumar, David F. Soria-Hernanz, Valampuri John Kavitha, Varatharajan Santhakumari Arun, Adhikarla Syama, Kumaran Samy Ashokan, Kavandanpatti Thangaraj Gandhirajan, Koothapuli Vijayakumar, Muthuswamy Narayanan, Mariakuttikan Jayalakshmi, Janet S. Ziegle, Ajay K. Royyuru, Laxmi Parida, R. Spencer Wells, Colin Renfrew, Theodore G. Schurr, Chris Tyler Smith, Daniel E. Platt, Ramasamy Pitchappan, The Genographic Consortiu

Castes, migration, immunogenetics and infectious diseases in South India

It has been said that the grandest genetic experiment of nature has been conducted in south India in the name of the caste system. One can expect the frequency of an infectious disease to be equal to the product of the frequencies of various indicated loci/alleles, whether physiological, hormonal or immunological, in an endemic area. The sympatrically isolated caste and sub-caste populations of southern India, with differing origins, migration patterns and breeding habits, differ significantly in their HLA and other immune repertoire and are ideal models to study and test this hypothesis. The prevalence of a number of major infectious diseases, including TB and leprosy, are reviewed in different communities in the light of their genetic history

Founder effects explain the distribution of the HLAA1-B17 but not the absence of the A1-B8 haplotypes in India

The HLA system may play an important role in natural selection processes through its involvement in immune response and because of the HLA association of some diseases. Linkage disequilibrium in the HLA system poses many interesting questions. India. a melting pot of races and cultures in sympatric isolation, provides an ideal opportunity to study these aspects. Linkage disequilibrium and haplotype data are valuable in the comparison of various populations. An analysis of the available HLA A-B haplotype data for the Indian population documents the heterogeneous nature of the latter: each endogamous caste group, major group or even regional group has its characteristic haplotype profile. The haplotypeA1-B17 is present in most Indian populations but A10-B8 occurs mostly in North India: this may be a consequence of founder effects. The haplotype Al-B8 a typical Caucasian haplotype, is absent in the Indian subcontinent: this may be due to the selective disadvantage A1-B8 confers in the Indian environment. The different regional and caste groups of India possessing diverse haplolype combinations provide an ideal opportunity to evaluate the selective values of these haplotypes and to study human immunogenetics

Diversity and dynamics of populations and disease susceptibility

“In an endemic environment, all susceptibles will develop the disease.“ South India, like the rest of the country is known for its caste system. The origin, level of inbreeding, endogamy and sympatric isolation amongst the caste system will lead to divergence of their gene pool and Ir (Immune response) genes are no exception to this. These differences may result in differential susceptibility at the population level. The lessons from inbred strains of animals explain this phenomenon and no immunologist or geneticist of today would like to carry out an experiment by mixing up the different strains of a species. In human populations in general, and in Indian caste groups in particular, the population dynamics like migration, miscegenation, social taboos and marriage patterns skew the picture and mask the differences between these populations particularly the prevalence and susceptibility to disease. Most of the research workers are disabled having a limited knowledge and even more limited facilities to do an 'ideal' experimental study in humans. Thus, in any clinical disease or immunological study in humans, a (case), caste, sex, nativity and haplotype (HLA or Ir gene) matched controls may need to be studied to understand the immunogenetic basis of disease susceptibility. The studies hitherto carried out at Madurai have revealed: i) different caste groups possess different haplotypes, some characteristic to a caste whereas others were common to many of them, ii) genetic distance calculated based on allele frequency brought out their affinity to each other; iii) not many Brahmin populations of India, have the same of the gene pool, presumably because of their origin, though they have all adopted the Hindu philosophy and religion, iv) numerically larger and geographically adjacent patrilineal clans of a tribe are genetically closer to each other; v ) a given HLA disease association transcend ethnic barrier (eg. pulmonary tuberculosis, leprosy), due to Ir gene dependant immunogeneric predisposition, vi) a few other HLA disease associations found in some populations or caste groups and not in others (eg. psoriasis) may be due to a linked gene and hitch hike phenomenon. Another new dimension is added to this genetic epidemiology: settlements, population size and the microbial world and infections increase in size as a function of time over the decades, resulting in faster transmission of a disease. The epidemiology is also changing over a period in the same place. As a result the newborn of today are subjected to a newer set of stress and selections than they were a generation ago. The epidemiology is known to affect the thymic education of lymphocytes through MHC, resulting in a different repertoire among children brought up in different environments. This has had great implications in subsequent environmental challenges and infections. Today any problem should be investigated and tackled by a group of open minded, knowledgeable scientists cutting across the barriers of their field of specializations. This is the need of the hour in this country