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PubMedDate not supplied

Apolipoproteins (apoproteins) and LPL variation in Mennonite populations of Kansas and Nebraska.

Apoproteins (also known as apolipoproteins) have been studied extensively because of their role in lipid transport, association between specific genotypes and elevated serum lipid levels, and increased risk of heart disease. There is considerable genetic variation in the geographic distributions of these markers, with a north-south cline of the APOE*4 allele observed in Europe by Lucotte et al. ([1997] Hum Biol 69:253-262). This study compares the frequencies of seven APO (APOA1 -75 bp, APOA1 +83 bp, APOB Ins/Del, APOB XbaI, APOC3 SstI, and APOE) and LPL loci in Mennonite populations from Kansas and Nebraska. In total, 277 individuals were sampled from Goessel, Meridian, Garden View, and Lone Tree in 2002-2004. In addition, DNA samples that were collected in 1981 from Henderson, Nebraska, were genotyped for the seven APO and LPL loci. Of the seven APO and LPL loci tested, only one locus, APOB XbaI, departed significantly from Hardy-Weinberg equilibrium, with an unexpected excess of observed heterozygotes. The frequencies of the several APO loci are unique among the Mennonites, separating them from other European populations. A bidimensional scaling representation of Reynold's co-ancestry distances based on allelic frequencies of the seven APO and LPL markers in five Mennonite congregations fails to represent schematically the known patterns of fission. It is unclear whether the observed patterns are due to selection operating on these loci or whether genetic drift, small populations sizes, or a lack of statistical power of these biallelic loci distort the observed genetic relationship among congregations.

Apolipoproteins↗
PubMed2005

Genome-wide SNP arrays as a diagnostic tool: clinical description, genetic mapping, and molecular characterization of Salla disease in an Old Order Mennonite population.

An Old Order Mennonite child was evaluated for gross motor delay, truncal ataxia, and slow linear growth. The diagnostic evaluation, which included sub-specialty consultations, neuroimaging, and metabolic testing, was long, costly, and did not yield a diagnosis. Recognition of a similarly affected second cousin prompted a genome-wide homozygosity mapping study using high-density single nucleotide polymorphism (SNP) arrays. SNP genotypes from two affected individuals and their parents were used to localize the disease locus to a 14.9 Mb region on chromosome 6. This region contained 55 genes, including SLC17A5, the gene encoding the lysosomal N-acetylneuraminic acid transport protein. Direct sequencing of SLC17A5 in the proband revealed homozygosity for the 115C --> T (R39C) sequence variant, the common cause of Salla disease in Finland. Three additional affected Mennonite individuals, ages 8 months to 50 years, were subsequently identified by directed molecular genetic testing. This small-scale mapping study was rapid, inexpensive, and analytically simple. In families with shared genetic heritage, genome-wide SNP arrays with relatively high marker density allow disease gene mapping studies to be incorporated into routine diagnostic evaluations.

Agenesis of Corpus Callosum↗
PubMed2003

Pediatric medicine and the genetic disorders of the Amish and Mennonite people of Pennsylvania.

The Clinic for Special Children in Lancaster County, Pennsylvania, is a community-supported, nonprofit pediatric medical practice for Amish and Mennonite children who have genetic disorders. Over a 14-year period, 1988-2002, we have encountered 39 heritable disorders among the Amish and 23 among the Mennonites. We emphasize early recognition and long-term medical care of children with genetic conditions. In the clinic laboratory we perform amino acid analyses by high-performance liquid chromatography (HPLC), organic acid analyses by gas chromatography/mass spectrometry (GC/MS), and molecular diagnoses and carrier tests by polymerase chain reaction (PCR) amplification and sequencing or restriction digestion. Regional hospitals and midwives routinely send whole-blood filter paper neonatal screens for tandem mass spectrometry and other modern analytical methods to detect 14 of the metabolic disorders found in these populations as part of the NeoGen Inc. Supplemental Newborn Screening Program (Pittsburgh, PA). Medical care based on disease pathophysiology reduces morbidity, mortality, and costs for the majority of disorders. Among our patients who are homozygous for the same mutation, differences in disease severity are not unusual. Clinical problems typically arise from the interaction of the underlying genetic disorder with common infections, malnutrition, injuries, and immune dysfunction that act through classical pathophysiological disease mechanisms to influence the natural history of disease.

Ethnicity↗
PubMed2003

Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania.

The Old Order Mennonites of southeastern Pennsylvania are a religious isolate with origins in 16th-century Switzerland. The Swiss Mennonites immigrated to Pennsylvania over a 50-year period in the early 18th century. The history of this population in the United States provides insight into the increased incidence of several genetic diseases, most notably maple syrup urine disease (MSUD), Hirschsprung disease (HSCR), and congenital nephrotic syndrome. A comparison between the Old Order Mennonites and the Old Order Amish demonstrates the unique genetic heritage of each group despite a common religious and geographic history. Unexpectedly, several diseases in both groups demonstrate allelic and/or locus heterogeneity. The population genetics of the 1312T --> A BCKDHA gene mutation, which causes classical MSUD, are presented in detail. The incidence of MSUD in the Old Order Mennonites is estimated to be 1/358 births, yielding a corrected carrier frequency of 7.96% and a mutation allele frequency of 4.15%. Analysis of the population demonstrates that repeated cycles of sampling effects, population bottlenecks, and subsequent genetic drift were important in shaping the current allele frequencies. A linkage disequilibrium analysis of 1312T --> A mutation haplotypes is provided and discussed in the context of the known genealogical history of the population. Finally, data from microsatellite marker genotyping within the Old Order Mennonite population are provided that show a significant but modest decrease in genetic diversity and elevated levels of background linkage disequilibrium.

Chromosomes, Human, Pair 19↗
PubMed2003

Anabaptist genealogy database.

In late 1996 we set out to build a computer-searchable genealogy of the Old Order Amish of Lancaster County, Pennsylvania, for use by geneticists. The goals of the project included: 1) using the genealogy to expedite the mapping of genes mutated in three rare recessive disorders under study at the National Institutes of Health (NIH); 2) building a freely available software package, PedHunter, to answer genetically relevant queries on our database and other similar databases; and 3) providing genealogy assistance to researchers outside NIH. All of these scientific goals had to be accomplished while maintaining the confidentiality of the persons in the database and the confidentiality of preliminary research results. We expanded the project to include complementary data sources that contained many individuals who were Anabaptist, but not Amish, and many individuals who never lived in Lancaster County. For this reason, the project was renamed Anabaptist Genealogy Database (AGDB). All of the initial goals of the project have been accomplished, and we recently marked the 5-year anniversary of answering the first of over 100 queries by researchers outside NIH. Thus, it is an opportune time to review the construction of AGDB, summarize its usage to date, and speculate on future projects it might stimulate and facilitate.

Databases, Genetic↗
PubMed2003

A study of linkage and association of body mass index in the Old Order Amish.

Obesity is thought to have a genetic component with the estimates of heritability ranging from 0.25-0.40. As part of an ongoing study of obesity in the Old Order Amish, seven two- and three-generation families (157 individuals) were assessed for 21 traits related to obesity, including body mass index (BMI) and BMI-percentile (a standardized distribution of BMI adjusted for age and sex). Genotyping was performed using a panel of 384 short-tandem repeat markers. In this sample, the estimates of heritability ranged from 0.16-0.31 for BMI and from 0.40-0.52 for BMI-percentile. Model-independent linkage analysis identified candidate regions on chromosomes 1, 5, 7, 8, and 11. Given that several markers on 7q were significant for both BMI and BMI-percentile (P < or = 0.001) and that the structural locus for leptin was located on 7q, this region was considered to be the primary candidate region. Subsequent typing of additional flanking markers on 7q corroborated the original findings. Tests of intrafamilial association for alleles at markers in this candidate region were significant at similar levels. Although there is some evidence for linkage and association in the region containing leptin, there appears to be stronger evidence for linkage (P < or = 0.001) and association (P < or = 0.00001) with BMI in a region 10-15 cM further downstream of leptin, flanked by markers D7S1804 and D7S3070 with peak values from D7S495-D7S1798. Evidence from linkage and association studies suggests that this region (D7S1804-D7S3070) may be responsible, at least in part, for variation in BMI and BMI-percentile in the Old Order Amish.

Alleles↗
PubMed2003

The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases.

Cartilage-hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia, was originally described in the Old Order Amish in the United States and subsequently found to be unusually frequent among Finns. The major mutation causing CHH in Finns is a 70A --> G nucleotide substitution in the RMRP gene, which encodes the untranslated RNA that is a component of mitochondrial RNA-processing endoribonuclease. Here we report that the same mutation is the most frequent one, perhaps the only one, in the Amish population in which CHH was first characterized. The fact that the mutation segregates with the same major haplotype in these two populations and others suggests that it is very ancient. Unlike some other ordinarily rare recessive disorders that are limited in their high frequency to a single Amish deme (subisolate), e.g., Ellis-van Creveld syndrome, CHH occurs in high frequency in at least three distinct Amish demes, indicating, along with genealogic data, that there were multiple heterozygotes among the founders, as proposed by McKusick et al. [1965: Bull Johns Hopkins Hosp 116:231-272].

Endoribonucleases↗
PubMed2003

[Pharmacy as a means of propagating the Lutherian doctrine of justification].

Pharmacy serving to propagate the Lutherian doctrine of justification: "Christus as a pharmacist" is an interconfessional, but confessionally differentiated symbolic motif (Sinnbildmotiv) of Christian folklore art in German-speaking countries. The article investigates the sociocultural conditions and prerequisites (German bible translation, religion and confession, piety, pharmacy, chymiatry, chemistry, apothecary training and status) for transfering the old metaphor and idea of Christ as a physician to the new vision of Christ as a apothecary who prepares and dispenses his heavenly medicine all by himself. In the early 17th century (especially in the 1610's) these requirements were fulfilled, so that the oldest known witness to this motif transfer (picturing the so-called Heilandsruf of Matthew 11, 28), a genre picture of 1619, will be the first pictural version of this motif in general. It was created by the protestant Painter Mich(a)el Herr of Nuremberg. In the abstract and reduced form of a devotional picture this motif then became widespread in churches and vicarages, in monasteries and their apothecaries as well as in private houses (with small altars: Herrgottswinkel). The oldest yet known examples are works from around 1630. For the first time during the Thirty Year's War, it served in this form for propagating the Lutherian justification doctrine (now referring to Jesaja 55, 1), saying that the belief in Christ is enough to be released from all sins (sola fide). Around 1650, as a reaction to that, a catholic version of the devotional picture was created, claiming and picturing that in contrast eucharist is the highest and real, healing medium' of Christ to redemption. All pictures of this version avoid quoting Jesaja 55, 1, whereas all protestant pictures quote this verse from the Bible word-for-word.

Germany↗
PubMed2003

[Pietism and medicine in the first half of the 18th century].

In the beginning of the 18th century Halle Pietists tried to establish a specific approach to sickness and healing. They constructed close links between physical illness on the one hand and the religious concept of individual piety, penance and rebirth on the other. This new' pietist medicine largely depended on Georg Ernst Stahl's medical theory, which was not pietist in itself, but was adopted and simplified by pietist physicians. Although conclusive and rhetorically present in programmatic texts, pietist medicine turned out to be less influential on medical practice than expected.

Germany↗
PubMed2004

Association between Protestant religiosity and obsessive-compulsive symptoms and cognitions.

There is evidence that religion and other cultural influences are associated with the presentation of obsessive-compulsive symptoms, as well as beliefs and assumptions presumed to underlie the development and maintenance of these symptoms. We sought to further examine the relationship between Protestant religiosity and (1) various symptoms of obsessive-compulsive disorder (OCD) (e.g., checking, washing) and (2) OCD-related cognitions. Using self-report questionnaires, we compared differences in these OCD-related phenomena between highly religious Protestants, moderately religious Protestants, and atheist/agnostic participants drawn from an undergraduate sample. Highly religious versus moderately religious Protestants reported greater obsessional symptoms, compulsive washing, and beliefs about the importance of thoughts. Additionally, the highly religious evinced more obsessional symptoms, compulsive washing, intolerance for uncertainty, need to control thoughts, beliefs about the importance of thoughts, and inflated responsibility, compared to atheists/agnostics. Results are discussed in terms of the relationship between religion and OCD symptoms in the context of the cognitive-behavioral conceptualization of OCD.

Adolescent↗
PubMed1993

Religion, medical ethics, and transplants.

This article describes the exclusion of public expressions of religion from the history of bioethics during recent decades. It offers a proposal to include the public church for the purpose of gaining donations of vital organs for transplantation. I also include a brief discussion of theological support and practical suggestions for such a program.

Black or African American↗