Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcγ receptors (FcγR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, λs > 10, purported linkage at 1q41–42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14–23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26–27, and 12p12–11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcγRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.

Microsatellites provide evidence for Y chromosome diversity among the founders of the New World

Recently, Y chromosome markers have begun to be used to study Native American origins. Available data have been interpreted as indicating that the colonizers of the New World carried a single founder haplotype. However, these early studies have been based on a few, mostly complex polymorphisms of insufficient resolution to determine whether observed diversity stems from admixture or diversity among the colonizers. Because the interpretation of Y chromosomal variation in the New World depends on founding diversity, it is important to develop marker systems with finer resolution. Here we evaluate the hypothesis of a single-founder Y haplotype for Amerinds by using 11 Y-specific markers in five Colombian Amerind populations. Two of these markers (DYS271, DYS287) are reliable indicators of admixture and detected three non-Amerind chromosomes in our sample. Two other markers (DYS199, M19) are single-nucleotide polymorphisms mostly restricted to Native Americans. The relatedness of chromosomes defined by these two markers was evaluated by constructing haplotypes with seven microsatellite loci (DYS388 to 394). The microsatellite backgrounds found on the two haplogroups defined by marker DYS199 demonstrate the existence of at least two Amerind founder haplotypes, one of them (carrying allele DYS199 T) largely restricted to Native Americans. The estimated age and distribution of these haplogroups places them among the founders of the New World.

Global survey of genetic variation in CCR5, RANTES, and MIP-1α: Impact on the epidemiology of the HIV-1 pandemic

Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, and its ligands (e.g., RANTES and MIP-1α) is widely regarded as central to the pathogenesis of HIV-1 infection. By surveying nearly 3,000 HIV+ and HIV− individuals from worldwide populations for polymorphisms in the genes encoding RANTES, MIP-1α, and CCR5, we show that the evolutionary histories of human populations have had a significant impact on the distribution of variation in these genes, and that this may be responsible, in part, for the heterogeneous nature of the epidemiology of the HIV-1 pandemic. The varied distribution of RANTES haplotypes (AC, GC, and AG) associated with population-specific HIV-1 transmission- and disease-modifying effects is a striking example. Homozygosity for the AC haplotype was associated with an increased risk of acquiring HIV-1 as well as accelerated disease progression in European Americans, but not in African Americans. Yet, the prevalence of the ancestral AC haplotype is high in individuals of African origin, but substantially lower in non-Africans. In a Japanese cohort, AG-containing RANTES haplotype pairs were associated with a delay in disease progression; however, we now show that their contribution to HIV-1 pathogenesis and epidemiology in other parts of the world is negligible because the AG haplotype is infrequent in non-Far East Asians. Thus, the varied distribution of RANTES, MIP-1α, and CCR5 haplotype pairs and their population-specific phenotypic effects on HIV-1 susceptibility and disease progression results in a complex pattern of biological determinants of HIV-1 epidemiology. These findings have important implications for the design, assessment, and implementation of effective HIV-1 intervention and prevention strategies.

A pre-Columbian Y chromosome-specific transition and its implications for human evolutionary history.

A polymorphic C-->T transition located on the human Y chromosome was found by the systematic comparative sequencing of Y-specific sequence-tagged sites by denaturing high-performance liquid chromatography. The results of genotyping representative global indigenous populations indicate that the locus is polymorphic exclusively within the Western Hemisphere. The pre-Columbian T allele occurs at > 90% frequency within the native South and Central American populations examined, while its occurrence in North America is approximately 50%. Concomitant genotyping at the polymorphic tetranucleotide microsatellite DYS19 locus revealed that the C-->T mutation displayed significant linkage disequilibrium with the 186-bp allele. The data suggest a single origin of linguistically diverse native Americans with subsequent haplotype differentiation within radiating indigenous populations as well as post-Columbian European and African gene flow. The mutation may have originated either in North America at a very early time during the expansion or before it, in the ancestral population(s) from which all Americans may have originated. The analysis of linkage of the DYS199 and the DYS19 tetranucleotide loci suggests that the C-->T mutation may have occurred around 30,000 years ago. We estimate the nucleotide diversity over 4.2 kb of the nonrecombining portion of the Y chromosome to be 0.00014. compared to autosomes, the majority of variation is due to the smaller effective population size of the Y chromosome rather than selective sweeps. There begins to emerge a pattern of pronounced geographical localization of Y-specific nucleotide substitution polymorphisms.

The African-American Islamic Renaissance and the Rise of the Nation of Islam

This dissertation examines African-American Islamic culture from 1920 through 1959, a period I label the "African-American Islamic Renaissance" (AAIR). The AAIR is characterized by a significant increase in interest in Islam, extreme diversity in views about Islam, and the absence of a single organization dominating African-American Islamic culture for a significant amount of time. Previous works dealing with African-American Islam in this period have failed to fully recognize these features, particularly the last of these. As a result, explanations for the rise of the Nation of Islam (NOI) have not satisfactorily explained why it was only the NOI--and not other Islamic groups that were more popular than the NOI up until the mid-1950s--that became a "mass movement," gaining the allegiance of tens of thousands of African Americans. There has been some tendency, for instance, to assume that the NOI was the most popular African-American Islamic group by the early 1950s, a notion that is probably an inference drawn from two other popular but inaccurate assumptions: that the NOI's rise was due primarily to its radical racialized doctrines and its charismatic leaders, particularly Malcolm X, who became a popular minister for the group in the early 1950s. I argue, however, that the NOI was in fact not the most popular African-American Islamic group until at least 1955, and even as late as 1959 its official membership numbers were not particularly large by AAIR standards. Also, its doctrines were not especially unique in the AAIR, nor was its having extremely charismatic leaders. I contend that the success of the NOI in the mid-to-late 1950s was the result of three levels of changes at the time: internal, external in the AAIR community, and external in the broader U.S, culture.

Brewing Behind Barbed Wire: An Archaeology of Saké at Amache

After the Japanese attack at Pearl Harbor on December 7, 1941, approximately 120,000 people of Japanese ancestry living on the west coast of the United States were forcibly removed from their home communities. These people were designated as "evacuees" by the U.S. Government and were incarcerated within a network of federal government facilities the largest of which were internment centers operated by the War Relocation Authority that held mostly U.S. citizens. The Granada Relocation Center (Amache) was the smallest of these internment centers. The presence of saké at Amache indicates that Japanese Americans continued important practices of daily life despite restrictions under confinement. This thesis investigates the practices of saké production and consumption at Amache and examines the importance of these practices in Japanese American daily life. In order to understand these practices, this research draws on multiple lines of evidence. This includes investigations of an assemblage of the material culture associated with saké, research into the history and methods of production and consumption, collection of oral histories, review of archival data, and the application of practice theory. These data provide insight into practices that are not well understood by researchers of Japanese American internment due to their illicit nature. This research endeavors to characterize how saké was produced and used at Amache and provides a way to understand how cultural practices maintain aspects of everyday life in ways that may have little to do with intentional resistance.

Wrestling With Tradition: Japanese Activities at Amache, a World War II Incarceration Facility

I employ archaeological analyses, archival research, and oral histories to investigate traditional Japanese practices that were performed at Amache, a World War II Japanese American incarceration facility. I argue that these inter-generational practices helped to bridge a cultural gap that existed between several generations of Japanese Americans. For many incarcerated Japanese Americans, their first exposure to many traditional activities occurred during incarceration. The resulting social environment incorporated aspects of Japanese, Japanese American, and mainstream American influences, all of which were adapted to conditions during incarceration. Similarly, archaeological analyses allow for the investigation of traditional practice features. These provide evidence regarding the significance of the adapted landscape at Amache. Evidence of these practices suggests Amache internees had both a strong desire to maintain and celebrate these aspects of their Japanese heritage but they also incorporated non-traditional elements that reflected the unique living conditions during incarceration. Incarceration, I argue, created an environment in which a unique internee consciousness was formed in which the use of traditional practices was a focal point. The physical remains of traditional practices allow archaeologists to determine aspects of this newly formed consciousness that are not readily apparent in historical documentation.

Blurring the lines : how Japanese American internment camps re-defined art and religion's relationship

After the Japanese bombed Pearl Harbor during WWII, anyone of Japanese descent living on the West Coast was placed in internment camps scattered throughout the country. Life inside the camps included many different activities to make life as normal as possible. This study will focus on two intersecting day-to-day activities in particular, the practice of religion within the camps, as well as the creation of art. Art created in the camps was influenced by multiple religious traditions. An analysis of artworks created by professional and amateur artists, interviews and an examination of existing scholarship demonstrates that internment camps created a unique environment for the creation of art. The values of internees reflected the seamless coexistence of Christianity, Buddhism and Shinto in internment camp art.

Looking Back: A Granddaughter's Quest for Redemption and Understanding

On December 7th, 1941 Japan attacked Pearl Harbor in Hawaii. This event signaled the beginning of America's involvement in World War II. It also signaled the beginning of a change of life for the Japanese living in the United States. Following the attack, 120,000 persons of Japanese ancestry were placed in ten internment camps across the United States. Two-thirds of those interned were American citizens, including my grandmother. The fact that these American citizens were treated as prisoners in their own country had a devastating effect on the relationships of those interned and the generations of Japanese Americans that followed. This essay recounts my grandma's experience and explores how her internment changed her life and the lives of her descendants.

Development of a Household Pharmaceutical Waste Collection Program for Atlanta, Georgia: An Analysis of Risk Factors and Public Awareness with a Comprehensive Collection Plan

Decades of mixed messages from three federal agencies left many Americans unaware of the hazards associated with the indiscriminate disposal of unwanted or expired medicines. For this Capstone project, a systematic review of state and federal regulations was undertaken to determine how these laws obstruct household pharmaceutical waste collection. In addition, a survey of 654 Atlanta residents was conducted to evaluate unwanted medicine disposal habits, awareness of pharmaceutical compounds being detected in drinking water, surface, and ground waters, and willingness to participate in a household pharmaceutical waste collection program. Survey responses were tabulated to provide overall results and by age group, gender, and race. A household pharmaceutical waste collection plan was developed for the city and included as an appendix.

Diaries of Benjamin Guild, 1776, 1778

These diaries of Benjamin Guild document his travels as a Presbyterian pastor in Massachusetts and Rhode Island. The daily entries describe people Guild met and dined with, the food he ate (including strawberries, currants, watermelon, English cherries, and lobster), the funerals he attended, and the sermons he gave. Many entries relate to his health concerns (the ague and eye trouble), sleeping habits, and widespread public health concerns (including smallpox, dysentery, "nervous fevers," consumption, and "putrid fever"). The diaries also contain passing references to the activities of American, British, French, and German soldiers during the American Revolution; the invasion of Canada and battles occurring in New York are noted. In August 1778, after visiting Providence, Rhode Island, Guild comments on the disordered state of the city after American soldiers passed through it. He also recounts a visit by officers of the French fleet to the Harvard College library in September 1778 and describes his dinner on board the French man-of-war, Sagitaire. One entry describes an elaborate ball sponsored by John Hancock, held for French soldiers and "Boston ladies," and another refers to the "incursion" of Indians. Many of Guild's diary entries pertain to his work as a Harvard College Tutor; these entries describe his lectures at the College, meetings with colleagues, personnel decisions, and the examination of students. He also describes books he is reading and his opinions of them, the purchase and sale of books, and his desire to learn Hebrew and French. In addition, multiple entries refer to a man named Prince, who was perhaps Guild's slave. Prince sometimes accompanied Guild on his travels.

Letters from William Tudor to Thomas Handasyd Perkins,

Four letters on topics including the Granite Railway project, Tudor’s thoughts on expanding trade in South America, domestic politics, and the process for appointing Americans to diplomatic posts.

Letters from Stephen Cassin to William Tudor,

One letter inquiring about Commodore John Orde Creighton, whom Cassin was replacing as commander of the naval squadron off the coast of Brazil. One letter asking Tudor’s advice on what action to take in regard to an altercation between two Americans and a Brazilian naval officer.

Manuscript on United States relations with England and France,

Parts nine through thirteen and postscript including transcriptions of contemporary London newspaper accounts of American naval maneuvers that Tudor believes are meant to portray Americans as "wholly destitute of veracity."