The takin and muskox: A molecular and ecological evaluation of relationship

Thesis (Ph.D.) University of Alaska Fairbanks, 1995This research clarifies the classification of and relationship between the takin (Budorcas taxicolor) and muskox (Ovibos moschatus). Although both are social ungulates of similar body size, takins live in dense mountainous habitats at temperate latitudes in Asia, and muskoxen live in open arctic habitats in Alaska, Canada and Greenland. Morphological, paleontological and chromosome comparisons have supported a close relationship between these species and their classification within the tribe Ovibovini in the subfamily Caprinae. Previous studies, however, have not defined the genetic relationship of the takin and muskox. This project used ecological and molecular comparisons to evaluate these proposed relationships. Ecological studies in Shaanxi, China showed takins are generalists in their use of habitat and forage, but live in dense habitat in groups, ostensibly to avoid predation. Likewise, muskoxen live in groups and are generalists, but inhabit open landscapes. Some ecological and behavioral similarities appear to support the hypothesis of close relationship. In contrast, molecular studies using cytochrome b sequences from mitochondrial DNA (mtDNA) clearly separate the takin and muskox into distinct clades. Takins are more closely related to sheep (Ovis spp.) and muskoxen to the Asian goral (Nemorhaedus caudatus). Similarities between the takin and muskox appear due to convergent evolution as an adaptation to large body size. A broader comparison of cytochrome b sequences from 11 species of Caprinae supported the separation of takins and muskoxen. Unequal rates of evolution among the species precluded complete resolution of Caprinae relationships. To define differences between muskox subspecies and populations, sequences of the highly variable control region of mtDNA from 37 muskoxen were compared. Delineation of muskox subspecies is a critical issue due to the potential for interbreeding of indigenous Canadian (O. m. moschatus) and introduced Alaskan (O. m. wardi) populations of muskoxen as range expansion occurs. Variability between these populations was so low differences could not be detected with this comparison. I suggest a history of genetic bottlenecks has reduced genetic variability of muskoxen to low levels and neither populations nor subspecies can be defined from control region sequences

A Case Study of Hispanic STEM Teacher Preparation

There is a shortage of Science, Technology, Engineering, and Mathematics (STEM) teachers in the US (Aragon, 2016; National Science Board, 2003). Hispanics are underrepresented in STEM teaching (Aragon, 2016; Texas Education Agency, 2017; US Census Bureau, 2016b; US Department of Education, n.d.). In order to improve the state of STEM teaching in the US we must tap into this underrepresented group. This exploratory case study examined the experiences of Hispanic students pursing STEM teacher preparation and how the UTeachRGV program impacts student persistence and retention. UTeachRGV is a STEM teacher preparation program at the University of Texas Rio Grande Valley (UTRGV) located in the southernmost region of Texas with a Hispanic population in the region that exceeds 90% (US Census Bureau, 2016b; UTRGV, 2016). UTRGV is designated a Hispanic Serving Institution (HSI) with a Hispanic student population that exceeds 89% and has a goal of serving these students as part of its vision (UTRGV, n.d; UTRGV, 2016). Sources of data included document analysis, an email questionnaire, focus groups, semi-structured interviews, and on-going field notes. All data were analyzed thematically within and across multiple data sources by searching for themes and subthemes. The major, overarching themes that emerged were support and shared experiences. Students benefitted from the support of Master Teachers, their UTeach family, and financial support. Students shared experiences in the program such as how they were recruited, why they stayed, the value of field experiences, and the supportive features of their HSI. Findings from the study indicate that Hispanic STEM students pursuing STEM teacher preparation within the context of UTeach experience systems of support and share experiences that contribute to their retention in the program. Findings suggest other STEM teacher preparation programs include incorporating multiple systems of support with mandatory advising checkpoints, faculty or other mentors, and financial support

Alaskan Marine Transgressions Record Out-of-Phase Arctic Ocean Glaciation During the Last Interglacial

Ongoing climate change focuses attention on the Arctic cryosphere’s responses to past and future climate states. Although it is now recognized the Arctic Ocean Basin was covered by ice sheets and their associated floating ice shelves several times during the Late Pleistocene, the timing and extent of these polar ice sheets remain uncertain. Here we relate a relict barrier-island system on the Beaufort Sea coast of northern Alaska to the isostatic effects of a previously unrecognized ice shelf grounded on the adjacent continental shelf. A new suite of optically stimulated luminescence dates show that this barrier system formed during one or more marine transgressions occurring late in Marine Isotope Stage 5 (MIS 5) between 113 ka and 71 ka. Because these transgressions occurred after the warmest part of the last interglacial (ca. 123 ka) and did not coincide with the global eustatic sea-level maximum during MIS 5e, this indicates Arctic ice sheets developed out-of-phase with lower-latitude sectors of the Laurentide and Fennoscandian ice sheets. We speculate that Arctic ice sheets began development during full interglacial conditions when abundant moisture penetrated to high latitudes, and low summer insolation favored glacier growth. These ice sheets reached their full extents at interglacial-glacial transitions, then wasted away at the heights of mid-latitude glaciations because of moisture limitations

Ice-age megafauna in Arctic Alaska: extinction, invasion, survival

Radical restructuring of the terrestrial, large mammal fauna living in arctic Alaska occurred between 14,000 and 10,000 years ago at the end of the last ice age. Steppe bison, horse, and woolly mammoth became extinct, moose and humans invaded, while muskox and caribou persisted. The ice age mega fauna was more diverse in species and possibly contained 6x more individual animals than live in the region today. Mega faunal biomass during the last ice age may have been 30x greater than present. Horse was the dominant species in terms of number of individuals. Lions, short-faced bears, wolves, and possibly grizzly bears comprised the predator/scavenger guild. The youngest mammoth so far discovered lived ca 13,800 years ago, while horses and bison persisted on the North Slope until at least 12,500 years ago during the Younger Dry as cold interval. The first people arrived on the North Slope ca 13,500 years ago. Bone-isotope measurements and foot-loading characteristics suggest mega faunal niches were segregated along a moisture gradient, with the surviving species (muskox and caribou) utilizing the warmer and moister portions of the vegetation mosaic. As the ice age ended, the moisture gradient shifted and eliminated habitats utilized by the dry land, grazing species (bison, horse, mammoth). The proximate cause for this change was regional paludification, the spread of organic soil horizons and peat. End-Pleistocene extinctions in arctic Alaska represent local, not global extinctions since the mega faunal species lost there persisted to later times elsewhere. Hunting seems unlikely as the cause of these extinctions, but it cannot be ruled out as the final blow to mega faunal populations that were already functionally extinct by the time humans arrived in the region

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations