Homozygosity mapping of the Achromatopsia locus in the Pingelapese.
Achromatopsia, or total color blindness (also referred to as "rod monochromacy"), is a severe retinal disorder characterized clinically by an inability to distinguish colors, impaired visual acuity in daylight, photophobia, and nystagmus. Inherited as an autosomal recessive trait, achromatopsia is rare in the general population (1:20,000-1:50,000). Among the Pingelapese people of the Eastern Caroline Islands, however, the disorder occurs at an extremely high frequency, as recounted in Oliver Sacks's popular book The Island of the Colorblind: 4%-10% of this island population have the disorder and approximately 30% carry the gene. This extraordinary enrichment of the disease allele most likely resulted from a sharp reduction in population in the late 18th century, in the aftermath of a typhoon and subsequent geographic and cultural isolation. To obtain insights into the genetic basis of achromatopsia, as well as into the genetic history of this region of Micronesia, a genomewide search for linkage was performed in three Pingelapese kindreds with achromatopsia. A two-step search was used with a DNA pooling strategy, followed by genotyping of individual family members. Genetic markers that displayed a shift toward homozygosity in the affected DNA pool were used to genotype individual members of the kindreds, and an achromatopsia locus was identified on 8q21-q22. A maximal multipoint LOD score of 9.5 was observed with marker D8S1707. Homozygosity was seen for three adjacent markers (D8S275, D8S1119, and D8S1707), whereas recombination was observed with the flanking markers D8S1757 and D8S270, defining the outer boundaries of the disease-gene locus that spans a distance of <6.5cM. (+info)
Thyroid nodules, thyroid function and dietary iodine in the Marshall islands.
BACKGROUND: Thyroid nodules have been found to be common in the population of the Marshall Islands. This has been attributed to potential exposure of radioiodines from the nuclear weapons tests on Bikini and Eniwetok between 1946 and 1958. METHODS: In order to get a full picture of thyroid pathology in the Marshallese population potentially exposed to radioactive fallout we performed a large thyroid screening programme using palpation, high resolution ultrasound and fine needle biopsies of palpable nodules. In addition, various parameters of thyroid function (free T3, free T4, thyroid stimulating hormone [TSH]) and anti-thyroid antibodies were examined in large proportions of the total population at risk. Since dietary iodine deficiency is an established risk factor for thyroid nodules, iodine concentration in urine samples of 362 adults and 119 children was measured as well as the iodine content of selected staple food products. RESULTS: The expected high prevalence of thyroid nodules was confirmed. There was no indication of an increased rate of impaired thyroid function in the Marshallese population. A moderate degree of iodine deficiency was found which may be responsible for some of the increased prevalence of thyroid nodules in the Marshallese population. CONCLUSIONS: Studies on the relationship between exposure to radioiodines and thyroid nodules need to take dietary iodine deficiency into account in the interpretation of findings. (+info)
A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study.
The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer. (+info)
Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins.
Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations. (+info)
Effects of chewing betel nut (Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia.
BACKGROUND: Although millions of people with schizophrenia live in betel chewing regions, the effects of betel chewing on their symptoms are unknown. Betel nut alkaloids include potent muscarinic cholinomimetics: recent research suggests that these agents may be therapeutic in schizophrenia. AIMS: To compare the primary and extrapyramidal symptom profiles and substance-using habits of betel chewing v. non-chewing people with schizophrenia. METHOD: A cross-sectional study of 70 people with schizophrenia. Symptom ratings measured by the Positive and Negative Syndrome Scale (PANSS) and Extrapyramidal Symptom Rating Scale (ESRS), and demographic and substance-use data, were compared for 40 chewers and 30 non-chewers of betel nut. RESULTS: Betel chewers with schizophrenia scored significantly lower on the positive (P = 0.001) and negative (P = 0.002) sub-scales of the PANSS than did non-chewers. There were no significant differences in extrapyramidal symptoms or tardive dyskinesia. CONCLUSIONS: Betel chewing is associated with milder symptomatology and avoidance of more harmful recreational drugs. These initial results indicate that longitudinal research is merited. (+info)
Epidemiology and factor analysis of obesity, type II diabetes, hypertension, and dyslipidemia (syndrome X) on the Island of Kosrae, Federated States of Micronesia.
OBJECTIVES: Obesity, type II diabetes, hypertension, and dyslipidemia are major causes of morbidity and mortality throughout the world. Though these disorders often cluster in individuals and families and are collectively known as syndrome X, the basis for this aggregation is not well understood. To further understand the pathogenesis of syndrome X, a comprehensive epidemiological study was undertaken on the Pacific Island of Kosrae, Federated States of Micronesia (FSM). METHODS: The entire adult (>20 years of age) population of Kosrae underwent a clinical evaluation that included a questionnaire that noted the participants' sex, family data including listing of biological parents, siblings, and children, smoking status, village of residence, age and health status. The medical evaluation included: anthropometric measures (weight, height, waist, hip), serum chemistries (leptin, fasting blood sugar (FBS), insulin, total cholesterol (TC), triglycerides (TG), and apolipoproteins B and A-I (apo B and apo A-I) and blood pressure (BP) measurements. RESULTS: Obesity (BMI >/=35) was found in 24%, diabetes (FBS >/=126 or 2-hour oral glucose tolerance test >/=200) in 12%, hypertension (SBP >/=140 or DBP >/=90) in 17%, and dyslipidemia (TC >/=240 or TG >/=200 or apo B >/=120 or apo A-I +info)
Retinol binding protein as a surrogate measure for serum retinol: studies in vitamin A-deficient children from the Republic of the Marshall Islands.
BACKGROUND: Serum retinol is transported by retinol binding protein (RBP), which has one high-affinity binding site for retinol; consequently, the molar ratio of retinol to RBP in the circulation is approximately 1 to 1. In vitamin A deficiency (VAD), both serum retinol and RBP decline. However, the retinol-RBP relation has not been well studied in populations with a high incidence of severe VAD. OBJECTIVE: The purpose of this study was to determine whether RBP is a good surrogate for serum retinol at the very low retinol concentrations encountered in VAD. DESIGN: The stoichiometric relation between retinol and RBP was studied in 239 Marshallese children: 65 with severe VAD (< or = 0.35 micromol retinol/L), 94 with moderate VAD (0.36-0.70 micromol retinol/L), and 80 with vitamin A sufficiency (> 0.70 micromol retinol/L). RESULTS: Excellent correlation between retinol and RBP (r = 0.94) was observed across all retinol concentrations. Severe VAD was predicted with 96% sensitivity and 91% specificity on the basis of an RBP cutoff of < or = 0.48 micromol/L, whereas moderate VAD was predicted with 87% sensitivity and 98% specificity on the basis of an RBP cutoff of < or = 0.70 micromol/L. CONCLUSIONS: The use of RBP results in the classification of essentially the same children with VAD as does retinol, and RBP is an excellent surrogate for serum retinol. Considering the relative ease of measuring RBP with immunodiagnostic kits compared with that of serum retinol by HPLC, the use of RBP concentrations to assess VAD may be particularly advantageous in field settings. Consequently, measuring RBP concentrations may be a practical alternative to measuring serum retinol in population surveys assessing the prevalence of VAD. (+info)
Vitamin A deficiency among children--Federated States of Micronesia, 2000.
Vitamin A, a fat-soluble, heat-stable nutrient (retinol) derived from animal sources and certain fruits and vegetables, forms the basic component of retinal pigments and plays a vital role in optimal health, growth, and development. Vitamin A deficiency (VAD) (serum retinol < or = 20 microg/dL [< or = 0.7 micromol/L] for subclinical VAD) can substantially increase the risk for childhood mortality from infectious and noninfectious causes. VAD impairs the mobilization and transport of iron and is usually associated with anemia and reduced growth. VAD is a major public health problem in parts of Africa, Asia, Latin America, and the Western Pacific. In Chuuk and Pohnpei, two of the four Federated States of Micronesia (FSM) (2000 population: 107,008), nutrition surveys during the early 1990s documented VAD prevalences among the highest in the world (CDC, unpublished data, 1991; U.S. Public Health Service, unpublished data, 1994). In response to these findings, FSM health authorities, with support of the United Nations Children's Fund (UNICEF), began distributing vitamin A supplements in 1993 and 1998 in Chuuk and Pohnpei, respectively. In November 1999, FSM requested assistance from CDC in VAD assessment surveys of children in Kosrae and Yap, the other two FSM states. This report summarizes levels of serum retinol and prevalence of VAD and other indicators of nutritional status among children aged 24-59 months in Kosrae and Yap. The findings indicated low serum retinol levels and high VAD prevalences but no substantial stunting or wasting. A comprehensive, long-term national strategy is needed in FSM to promote sustained improvement in vitamin A status. (+info)