Present study was planned to compare the phenotypic variation of performances traits among commercial (CC) and heritage varieties of turkeys. Information about heritage turkey varieties continues to be limited. In addition, the emerging turkey genome sequence provides a unique opportunity to understand the DNA sequence variation and its associations with performance traits. The turClock, turPer3, turCry1 and turCry2 genes were screened and evaluated for its association with their performance traits. As expected, CC turkeys were superior to heritage birds in performance for most of the traits evaluated. However, heritage turkeys showed better reproductive performances compared to CC turkeys. A total of 41 SNPs were identified from the genes that screened. The haplogroups in the turClock gene were significantly associated with body weight (BW) at 309 d of age, feed conversion ratio (FCR) for 34 - 68 d and 69 - 159 d, egg production and average egg weight (P " 0.05). The haplogroups developed from turPeriod-3 gene were significantly associated with BW at 231 d of age, average daily gain (ADG) for 160 - 231 d, FCR for 69 - 159 d and 160 - 231 d, egg production traits, semen quality traits and plasma melatonin concentration (P " 0.05). In the turCry1 gene, haplogroups were significantly associated with ADG for 35 - 68 d, FCR for 160 - 231 d and 34 - 231 d, egg production and ejaculate volume (P " 0.05). The haplogroups identified from turCry2 gene were significantly associated with BW at 34, 68 and 231 d of age, ADG for 160 - 231 d, FCR for 34 - 68 d, average egg weight (P " 0.05). These findings reveal that phenotypic variation observed in growth and reproductive parameters among turkeys could be used for selecting birds for future breeding programs. DNA sequence variations at the nucleotide and haplotype levels are associated with some of growth, reproductive parameters and plasma melatonin of turkeys. Thus DNA sequence variations that identified of the circadian genes may have some regulatory role in the molecular mechanism of the circadian clock which may affect the circadian rhythm of the animal. / Ph. D.

BACKGROUND: Uruguay exhibits one of the highest rates of breast cancer in Latin America, similar to those of developed nations, the reasons for which are not completely understood. In this study we investigated the effect that ancestral background has on breast cancer susceptibility among Uruguayan women. METHODS: We carried out a case-control study of 328 (164 cases, 164 controls) women enrolled in public hospitals and private clinics across the country. We estimated ancestral proportions using a panel of nuclear and mitochondrial ancestry informative markers (AIMs) and tested their association with breast cancer risk. RESULTS: Nuclear individual ancestry in cases was (mean ± SD) 9.8 ± 7.6% African, 13.2 ± 10.2% Native American and 77.1 ± 13.1% European, and in controls 9.1 ± 7.5% African, 14.7 ± 11.2% Native American and 76.2 ± 14.2% European. There was no evidence of a difference in nuclear or mitochondrial ancestry between cases and controls. However, European mitochondrial haplogroup H was associated with breast cancer (OR = 2.0; 95% CI 1.1, 3.5). CONCLUSIONS: We have not found evidence that overall genetic ancestry differs between breast cancer patients and controls in Uruguay but we detected an association of the disease with a European mitochondrial lineage, which warrants further investigation.

The thesis is focused on two mtDNA haplogroups of Eurasian origin that occur mostly among the Fulani, herders of the African Sahel. On the initial analysis 544 DNA samples from unrelated Fulani individuals were used. These samples were classified to haplogroups according to hypervariable segment I (HVS-I) of mtDNA and subsequently, specific Eurasian haplotypes were chosen for the whole mtDNA genome sequencing. Obtained mito-genomes were assigned to phylogenetic trees and dated. It turned out that they belonged to haplogroups U5b1b1b and H1ca1a with the probable origin in the Iberian Peninsula, presumably in Franco-Cantabrian refugium where their ancestors originated in the period between the Late Glacial and the first half of the Holocene. Afterwards they migrated through the Strait of Gibraltar to North Africa and the Sahara, where the proto-Fulani pastoral population was being formed. It may also be assumed that a part of this population came to Africa from the Near East, along with cattle. In the second half of the Holocene, this pastoral population migrated from the drying Sahara to the Sahel. Probably due to small number of female migrants the females from the local populations were integrated, which explains the major representation of West African mtDNA haplogroups in contemporary Fulani....

>Magister Scientiae - MSc / The objective of this study is to deduce paternal ancestry using ancestry informative single nucleotide polymorphisms (SNPs) by means of High Resolution Melting (HRM). This was completed by producing a multiplex system that was designed in a hierarchical manner according to the YSNP tree. This project mainly focused on African ancestry and was used to infer paternal ancestral lineages on the Johannesburg Coloured population. South Africa has a diverse population that has ancestral history from across the globe. The South African Coloured population is the most admixed population as it is derived from at least five different population groups: these being Khoisan, Bantu, Europeans, Indians and Southeast Asians. There have been studies done on the Western Cape/ Cape Town Coloured populations before but this study focused on the Johannesburg Coloured population.

Magister Scientiae - MSc (Biotechnology) / The objective of this study is to deduce paternal ancestry using ancestry informative single nucleotide polymorphisms (SNPs) by means of High Resolution Melting (HRM). This was completed by producing a multiplex system that was designed in a hierarchical manner according to the YSNP tree. This project mainly focused on African ancestry and was used to infer paternal ancestral lineages on the Johannesburg Coloured population. South Africa has a diverse population that has ancestral history from across the globe. The South African Coloured population is the most admixed population as it is derived from at least five different population groups: these being Khoisan, Bantu, Europeans, Indians and Southeast Asians. There have been studies done on the Western Cape/ Cape Town Coloured populations before but this study focused on the Johannesburg Coloured population. The first step was to design the multiplex system. This was done by using inhouse SNPs. A total of seven multiplexes were designed and optimised, each consisting of two, three or four different SNPs respectively. A total of 143 saliva and buccal samples were collected from male Johannesburg Coloureds. DNA was extracted from the saliva samples using an optimised organic method. DNA was extracted from the buccal samples using an optimised salting out method. DNA was successfully extracted from 77 of the male samples. A total of 69 samples were screened using Multiplex 1; of the 69 samples 56 samples were successfully screened to infer the paternal lineage of the samples. The results show that the most frequent haplogroup of the Johannesburg male samples was haplogroup CF (39%). The second most frequent haplogroup was haplogroup DE (38%). Under further analysis of haplogroup DE it was seen that 37% of those samples were derived for the haplogroup E1b1b.

In the present study, history of domestic sheep were investigated by mitochondrial DNA (mtDNA) based haplogroups (HPG) of 628 samples and mtDNA control region (CR) sequences of 240 samples from 13 Turkish sheep breeds which were located in the hearth of the first domestication center. Also, 30 Anatolian wild sheep (Ovis gmelinii anatolica) mtDNA CR sequences were obtained to contribute to the scenarios on initial domestication stages of sheep. Haplogroup compositions of breeds were identified with SSCP method by using mtDNA ND2 region. The genetic diversity and relationship between haplogroups were calculated. Phylogenetic analyses of haplogroups such as median joining networks and neighbor joining trees were constructed for mtDNA CR, cytochrome B (cytB) and combined CR-cytB sequences with sequences from the present study together with sequences retrieved from NCBI (http://www.ncbi.nlm.nih.gov/). Results of the present study showed that all previously observed haplogroups (HPG A-E) were present in Turkish sheep breeds. Two individuals from rare HPG D and eleven individuals from rare HPG E were detected and sequenced. With increased sample size, for HPG E, past population expansion was observed as was the case of HPG A, B and C with mismatch distributions and neutrality tests. Spatial autocorrelation analyses and synthetic map with respect to mtDNA (maternal) pattern revealed that Turkey was separated into two regions which may be attributed to the imprints of third migration of sheep associated with the arrivals of nomadic Turks to Anatolia nearly 1000 years before present. Finally, Ovis gmelinii anatolica samples exhibited two haplotypes / one of them belongs to HPG A (possibly feral domesticate), and the other one shows a distinct haplotype (close to HPG E and C) that was not observed before. Observed, low mtDNA diversity might be the result of isolation, fragmentation, extinction of fragments and bottlenecks. Ovis gmelinii anatolica can be part of the evolved descendants of the wild sheep which gave birth to the domestic sheep.

Breast cancer is the most common cancer type in the United Kingdom. Many women with breast cancer do not show any noticeable symptoms in their early stages, hence regular breast screening is important. In this research focus is on medical imaging and its role in breast cancer screening, diagnosis, and treatment monitoring. Around 10% of all cancers are caused by inherited gene mutations which may cause cancer to run in families. Though, majority of cancer cases (up to 90%) are caused by acquired gene mutations which may also appear to run in families when family members share a particular environment or exposure. Genetic testing is conducted in this research on a number of participants to investigate the cancer cases found among their families. The findings of this research show that significant improvements have taken place in the emergence of hybrid imaging modalities used for breast imaging, through the fusion of different imaging techniques. The findings also provide evidence that similar to cancers caused by inherited gene mutations, cancers caused by non-inherited gene mutations may also appear to run in families when family members share certain environments and exposures or lifestyle behaviours. As a result, a new genetic concept of cancer essential to understand and control the disease is presented in this work which links between the human population origins and migrations, environmental factors and gene mutations, and the development of cancer. Furthermore, a number of cancer prevention strategies are recommended in this study to prevent people from getting the disease.

Markers on the non-recombining region of chromosome Y is a useful tool for study of diversity between populations. SNPs are the most commom polymorphisms in human genome. Mutation rate of SNPs is very low and so they may be used as genetic markers in evolutionary and population studies. We have analyzed 205 unrelated men from 11 Sub-Saharan Fulani's subpopulations. Fulani are an ethnic group of people spread over many countries, mainly in West Africa. Our samples are from Tindangou area, Banfora area (Burkina Faso), Bongor area, Linia area (Chad), Diafarabé area (Mali), Tcheboua area (Cameroon), Banfora area, Diffa area, Zinder area, Ader area and Abalak area (Niger). Using kit Signet Y-SNP Identification Systems and Luminex instrument with LabMAP Luminex Technology we detected particular Y chromosome's SNPs. LabMAP Luminex Technology is universal array platform, which as a probe using fluorescent polystyrene microspheres. We have observed 12 different haplogroups. Haplogroup E, which is typical African haplogroups, is determined with derivated allele in polymorfism M96. We have detected haplogroup E in maximum of 89,3% in the Fulani's subpopulations. In 7,8% we have detected haplogroup R, which is characteristic of populations in the Euroasia. Gene pool of Fulani's population is influenced with a...

Les mitochondries, organelles intracellulaires des eucaryotes, fournissent par les oxydations phosphorylantes l'essentiel de l'énergie nécessaire aux différents travaux cellulaires sous la forme d'ATP grâce à un couplage entre la chaîne respiratoire et l’ATPsynthase. Ces réactions du métabolisme énergétique sont assurées par des complexes enzymatiques constitués de sous-unités codées à la fois par l'ADN nucléaire et par l'ADN mitochondrial. Il a été montré que des défauts dans l'activité de ces complexes pouvaient être responsables de l’apparition de pathologies regroupées sous le nom de cytopathies d’origine mitochondriale. Un des problèmes fondamentaux qui se pose lors de l’étude des mécanismes conduisant aux pathologies mitochondriales est de comprendre l’influence de l’ADN mitochondrial sur le métabolisme de la mitochondrie. En effet, la mitochondrie possède son propre ADN, et les mutations de cet ADN sont classées selon leur impact sur le métabolisme mitochondrial : des mutations pathogènes, qui ont des répercussions négatives sur ce métabolisme, et des polymorphismes, qui sont considérés comme étant neutres.Pour étudier l’influence de l’ADNmt sur le métabolisme énergétique, j’ai utilisé deux modèles d’étude : des cybrids portant des mutations de l’ADNmt retrouvées chez des patients atteints de surdité non-syndromique, et des cybrids portant des polymorphismes caractéristiques de l’haplogroupe J.Les résultats obtenus nous indiquent clairement que la différence entre des mutations pathogènes et des polymorphismes n’est pas aussi importante que ce qui était jusqu’à alors supposé. En effet, elle dépend d’un ensemble de facteurs tels que (i) le fonds génétique nucléaire et mitochondrial, (ii) de facteurs environnementaux. Car sous l’influence de ces différents facteurs une mutation considérée comme pathogène peut devenir neutre, et un polymorphisme considéré comme neutre peut devenir pathogène. / Mitochondria, intracellular organelles of eukaryotic organisms, provide most of the necessary energy for cellular activity through oxidative phosphorylation, synthesizing ATP (energy source for the cell) by a coupling between the respiratory chain and the ATPsynthase. These energy metabolism reactions are carried out by enzymatic complexes constituted by sub-units coded by both nuclear and mitochondrial DNA. It has been shown that activity defects in these complexes could be responsible for a group of pathologies under the name of mitochondrial cytopathies.One of the fundamental issues of the study of the mechanisms that lead to mitochondrial cytopathies is the understanding of the influence that mitochondrial DNA has over mitochondrial metabolism. Indeed, mitochondria have their own DNA, and mutations in this DNA are classified according to their impact on mitochondrial metabolism: pathological mutations, which have negative consequences on mitochondrial metabolism, and polymorphisms, which are considered to be neutral.In order to study the influence of mtDNA on energy metabolism, I used two different models: cybrid cells carrying mtDNA mutations found in non-syndromic hearing loss patients, and cybrid cells carrying polymorphisms defining haplogroup J.The results gathered in these studies show that the difference between pathological mutations and polymorphisms is not as big as previously believed. Indeed, it depends on several factors, such as the nuclear and mitochondrial genetic backgrounds, as well as the environmental factors, because under the influence of these factors a mutation considered as pathological may become neutral, and a polymorphism considered neutral may become pathological.

Une large part de la composante génétique du risque de cancer du sein est encore inexpliquée. J'ai ainsi étudié dans quelle mesure les variants observés sur le génome mitochondrial pourraient en partie expliquer ce risque. En effet la mitochondrie, en tant que source d'énergie cellulaire, est un organite impliqué dans la synthèse des espèces oxygénées réactives ou radicaux libres, éléments contribuant à l'instabilité génomique et au développement tumoral. Un premier axe de recherche m'a conduit à étudier une interaction potentielle entre des variants du génome mitochondrial et du génome nucléaire, en conjonction avec la consommation d'alcool. J'ai ensuite analysé les haplogroupes mitochondriaux peuvent être considérés en tant que potentiels modificateurs de l'association entre le risque de cancer du sein et les mutations causales portées par les gènes BRCA1 et BRCA2. L'haplogroupe T1a1 a été identifié comme modificateur du risque conféré par les mutations pathogènes localisées sur le gène BRCA2. Enfin, j'ai caractérisé par séquençage à haut débit le génome mitochondrial de 436 femmes ayant un cancer du sein et de forts antécédents familiaux, mais n'étant porteuses d'aucune mutation causale sur BRCA1 et BRCA2. Plusieurs variants ont été prédits comme dommageables. Deux gènes en particulier MT-ATP6 et MT-CYB, sont spécifiquement enrichis à la fois en nombre de variants portés, et de par le nombre d'individus porteurs de ces variants dans notre étude. L'ensemble du travail réalisé a ainsi contribué à enrichir les connaissances sur les potentielles associations entre les variations du génome mitochondrial et le risque du cancer du sein / A large part of the genetic component of breast cancer risk (BCR) is still unexplained. Therefore I studied if variants of the mitochondrial genome (mtDNA) might explain a part of this risk. In fact, mitochondria is the main source of reactive oxygen species (ROS), which contribute to genomic instability and tumor development. As a first axis of research, I studied potential interactions between some nuclear and mitochondrial variants, in conjugation to alcohol consumption. Despite the large dimensions of our dataset, the lack of statistical significant interaction in our data might reveal that former published results that show such interactions were not robust. I also studied if mitochondrial haplogroups could be considered as modificators of known association between BCR and pathogenic mutations in the BRCA1/2 genes. I identified haplogroup T1a1 such as modificator for individuals carrying a mutated BRCA2. Finally, I characterized by NGS mitochondrial genome of women diagnosed for a familial breast cancer, but tested negative for known pathogenic BRCA1/2 mutations. Several variants were identified as potentially damaging. Two genes, MT-ATP6 and MT-CYB are specifically enriched both in terms of distinct variants and in the number of individuals carrying these variants. They are both essential structural components of the mitochondrial respiratory chain, the main ROS production source in the cell. All these analyses contribute to enrich the knowledge about associations between BCR and variability of mtDNA, by integrating questions linked to interactions between genomic variants, environmental exposure, and effect modifications related to mitochondrial haplogroups