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Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of

Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of linkage disequilibrium and the persistence of deleterious mutations. This has led to an increased susceptibility to a multitude of diseases, including cancer. To study the effects of artificial selection and life history characteristics on the risk of cancer mortality, we collected cancer mortality data from four studies as well as the percent of heterozygosity, body size, lifespan and breed group for 201 dog breeds. We also collected specific types of cancer breeds were susceptible to and compared the dog cancer mortality patterns to the patterns observed in other mammals. We found a relationship between cancer mortality rate and heterozygosity, body size, lifespan as well as breed group. Higher levels of heterozygosity were also associated with longer lifespan. These results indicate larger breeds, such as Irish Water Spaniels, Flat-coated Retrievers and Bernese Mountain Dogs, are more susceptible to cancer, with lower heterozygosity and lifespan. These breeds are also more susceptible to sarcomas, as opposed to carcinomas in smaller breeds, such as Miniature Pinschers, Chihuahuas, and Pekingese. Other mammals show that larger and long-lived animals have decreased cancer mortality, however, within dog breeds, the opposite relationship is observed. These relationships could be due to the trade-off between cellular maintenance and growing fast and large, with higher expression of growth factors, such as IGF-1. This study further demonstrates the relationships between cancer mortality, heterozygosity, and life history traits and exhibits dogs as an important model organism for understanding the relationship between genetics and health.
ContributorsBalsley, Cassandra Sierra (Author) / Maley, Carlo (Thesis director) / Wynne, Clive (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to

Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to previous findings in elephants, bats have experienced duplications of the tumor suppressor gene TP53, including five genomic copies in the genome of the little brown bat (Myotis lucifugus) and two copies in Brandt's bat (Myotis brandtii). These species can live 37 and 41 years, respectively, despite having an adult body mass of only ~7 grams. We use evolutionary genetics and next generation sequencing approaches to show that positive selection has acted on the TP53 locus across bats, and two recently duplicated TP53 gene copies in the little brown bat are both highly conserved and expressed, suggesting they are functional. We also report an extraordinary genomic copy number expansion of the tumor suppressor gene FBXO31 in the common ancestor of vesper bats which accelerated in the Myotis lineage, leading to 34\u201457 copies and the expression of 20 functional FBXO31 homologs in Brandt's bat. As FBXO31 directs the degradation of MDM2, which is a negative regulator of TP53, we suggest that increased expression of both FBXO31 and TP53 may be related to an enhanced DNA-damage response to genotoxic stress brought on by long lifespans and rapid metabolic rates in bats.
ContributorsSchneider-Utaka, Aika Kunigunda (Author) / Maley, Carlo (Thesis director) / Wilson Sayres, Melissa (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description

Agassiz’s desert tortoise (Gopherus agassizii) is a long-lived species native to the Mojave Desert and is listed as threatened under the US Endangered Species Act. To aid conservation efforts for preserving the genetic diversity of this species, we generated a whole genome reference sequence with an annotation based on dee

Agassiz’s desert tortoise (Gopherus agassizii) is a long-lived species native to the Mojave Desert and is listed as threatened under the US Endangered Species Act. To aid conservation efforts for preserving the genetic diversity of this species, we generated a whole genome reference sequence with an annotation based on deep transcriptome sequences of adult skeletal muscle, lung, brain, and blood. The draft genome assembly for G. agassizii has a scaffold N50 length of 252 kbp and a total length of 2.4 Gbp. Genome annotation reveals 20,172 protein-coding genes in the G. agassizii assembly, and that gene structure is more similar to chicken than other turtles. We provide a series of comparative analyses demonstrating (1) that turtles are among the slowest-evolving genome-enabled reptiles, (2) amino acid changes in genes controlling desert tortoise traits such as shell development, longevity and osmoregulation, and (3) fixed variants across the Gopherus species complex in genes related to desert adaptations, including circadian rhythm and innate immune response. This G. agassizii genome reference and annotation is the first such resource for any tortoise, and will serve as a foundation for future analysis of the genetic basis of adaptations to the desert environment, allow for investigation into genomic factors affecting tortoise health, disease and longevity, and serve as a valuable resource for additional studies in this species complex.

Data Availability: All genomic and transcriptomic sequence files are available from the NIH-NCBI BioProject database (accession numbers PRJNA352725, PRJNA352726, and PRJNA281763). All genome assembly, transcriptome assembly, predicted protein, transcript, genome annotation, repeatmasker, phylogenetic trees, .vcf and GO enrichment files are available on Harvard Dataverse (doi:10.7910/DVN/EH2S9K).

ContributorsTollis, Marc (Author) / DeNardo, Dale F (Author) / Cornelius, John A (Author) / Dolby, Greer A (Author) / Edwards, Taylor (Author) / Henen, Brian T. (Author) / Karl, Alice E. (Author) / Murphy, Robert W. (Author) / Kusumi, Kenro (Author)
Created2017-05-31
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Walter Schiller studied the causes of diseases in the US and Austria in the early twentieth century and in 1928, invented the Schiller test, or a way to diagnose early cervical cancer in women. Cervical cancer is the uncontrollable division of cells in the cervix, or lower part of the

Walter Schiller studied the causes of diseases in the US and Austria in the early twentieth century and in 1928, invented the Schiller test, or a way to diagnose early cervical cancer in women. Cervical cancer is the uncontrollable division of cells in the cervix, or lower part of the uterus. While living in Austria until his emigration to escape the Nazis in 1937, Schiller concluded that there was a form of cervical cancer, later named carcinoma in situ, that physicians could detect earlier than when tumors start to appear. To determine whether women exhibited that early form of cancer, Schiller stained women’s cervixes with a type of iodine that would stain healthy cervical tissue and not cancerous cervical tissue. Cervical cancer is more deadly to women when it is caught later in its progression, and was difficult to detect in Schiller's time. Schiller’s research enabled physicians to diagnose cervical cancer early, helping women receive treatment quicker and ultimately helping to popularize annual diagnostic exams in the US.

Created2021-08-12
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In 1913, journalist Samuel Hopkins Adams published “What Can We Do About Cancer? The Most Vital and Insistent Question in the Medical World,” hereafter “What Can We Do About Cancer,” in Ladies’ Home Journal. Cancer is a disease that is the result of abnormal cell division in different parts of

In 1913, journalist Samuel Hopkins Adams published “What Can We Do About Cancer? The Most Vital and Insistent Question in the Medical World,” hereafter “What Can We Do About Cancer,” in Ladies’ Home Journal. Cancer is a disease that is the result of abnormal cell division in different parts of the body, such as the breasts or the cervix. During that time, many women did not discuss or disclose early symptoms of reproductive cancers, such as breast lumps and abnormal vaginal discharge, out of shame or disgust. Thus, people often considered cancer to be a taboo topic. “What Can We Do About Cancer?” provides a representation of what people in the early 1900s thought to be the early warning signs of cancer in women. Although, as of 2021, researchers have made advancements that have increased the scientific understanding of cancer and how it develops, Adams’ article provided women in the US during the 1900s with recommendations on early methods of cancer detection.

Created2021-08-02
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In 2017, Angiolo Gadducci, Silvestro Carinelli, and Giovanni Aletti published, "Neuroendocrine Tumor of the Uterine Cervix: A Therapeutic Challenge for Gynecologic Oncologists," hereafter, "Neuroendocrine Tumor" in the journal, Gynecologic Oncology. The authors conducted a systematic review of existing literature that documented the symptoms, diagnosis, staging, treatment, and outcomes of women

In 2017, Angiolo Gadducci, Silvestro Carinelli, and Giovanni Aletti published, "Neuroendocrine Tumor of the Uterine Cervix: A Therapeutic Challenge for Gynecologic Oncologists," hereafter, "Neuroendocrine Tumor" in the journal, Gynecologic Oncology. The authors conducted a systematic review of existing literature that documented the symptoms, diagnosis, staging, treatment, and outcomes of women diagnosed with neuroendocrine tumors, or cervical NETs, which are tumors with cells similar to cells from both the hormonal and the nervous system. Based on high mortality rates and the rarity of cervical NET diagnoses, the authors conclude that cervical NETs present a challenge for physicians in terms of devising novel ideas for treatment. By compiling the treatment methods and resulting outcomes of different studies, the authors presented evidence that there is a need for new forms of treatment to reduce the number of women dying from cervical NETs each year.

Created2022-04-16
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This thesis answers the following question: How does the history of cervical cancer show that prevention helps reduce rates of cancer-related deaths among women? By studying the history of cervical cancer, people can understand how a cancer that was once one of the top killers of women in the US

This thesis answers the following question: How does the history of cervical cancer show that prevention helps reduce rates of cancer-related deaths among women? By studying the history of cervical cancer, people can understand how a cancer that was once one of the top killers of women in the US has declined to become one of the lowest through the establishment of and effective communication of early prevention and diagnostics, both among the general public and within the medical community itself. This thesis is organized based on key episodes which were pertinent to the history of cervical cancer, primarily within the United States and Europe.

Created2021-03-22
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From 1936 to 1945, the Women’s Field Army, hereafter the WFA, educated women in the US on the early symptoms, prevention, and treatment of reproductive cancers. The WFA was a women-led volunteer organization and a branch of, what was then called, the American Society for the Control of Cancer, or

From 1936 to 1945, the Women’s Field Army, hereafter the WFA, educated women in the US on the early symptoms, prevention, and treatment of reproductive cancers. The WFA was a women-led volunteer organization and a branch of, what was then called, the American Society for the Control of Cancer, or ASCC. The WFA, headquartered in New York City, New York, recruited hundreds of thousands of women volunteers across the country. They distributed pamphlets, showed movies, and participated in other grassroots efforts to foster an understanding of reproductive cancers, namely breast and cervical cancer, among other women. The Women’s Field Army aided in reducing the number of cancer-related deaths by spreading cancer prevention awareness and teaching women about their reproductive health and the early detection of cancer, which was one of the first widespread educational resources about reproductive cancers for women.

Created2021-07-31