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PubMed1995

Varicella zoster virus and multiple sclerosis in a Hutterite population.

There are similarities between multiple sclerosis and varicella. They are common in the same parts of the world and both are scarce in other areas. Immigration studies suggest the environmental cause of multiple sclerosis (MS) must be contracted prior to age 15 years and will usually remain dormant for years. At age 10 years varicella has occurred in greater than 95% of children living in the high-risk areas for both of these diseases. The varicella zoster virus (VZV) could be etiologically important in multiple sclerosis. The known host containment of the virus for decades with recrudescence and the variable cell-mediated immunity of the host, which can wax and wane without clinical manifestations, all lend themselves to the natural history of multiple sclerosis. A population-based study of the medical records of 5601 Hutterite Brethren was performed to determine the occurrence of multiple sclerosis, varicella, and herpes zoster. Compared to their matched non-Hutterite neighbors who acted as controls, these events were significantly less common among the Hutterites. Included in the study was an assessment of other common neurological diseases and "autoimmune" diseases among the Hutterites and the controls. There is evidence of a relationship between MS and VZV that may not be coincidental.

Adolescent↗

PubMed2000

Polymorphisms in the HLA-linked olfactory receptor genes in the Hutterites.

Genes in the MHC have been associated with mate choice and odor preferences in a variety of animals. Although the role of HLA genes in human mate choice has been controversial, studies in the Hutterites have demonstrated fewer than expected numbers of couples who match for an HLA haplotype, suggesting that in this population there is avoidance of mates with HLA haplotypes similar to one's own haplotype. Recently, 18 olfactory receptor (OR) genes have been mapped to the HLA region, telomeric to the HLA-F locus, providing a potential mechanism for HLA-based odor recognition and perhaps mate preferences in humans. We screened a sample of Hutterites with diverse HLA haplotypes for polymorphisms in the HLA-linked olfactory receptor gene, FAT11, by sequencing, denaturing high performance liquid chromatography, and allele-specific oligo dot-blotting. Three single nucleotide polymorphisms were detected in the single translated exon of this gene, all of which resulted in amino acid substitutions (Phe587Leu, Ala642Val, and Thr1157Ala). The FAT11 Phe587- Val642-Ala1157 allele occurred on 17 different HLA haplotypes, the Leu587-Ala642-Ala1157 allele on 15 haplotypes, the Phe587-Ala642-Ala1157 allele on 16 haplotypes, and the Phe587-Ala642-Thr1157 allele on a single haplotype. Thus, four alleles of the FAT11 gene are present in the Hutterites. This level of variation in the FAT11 gene alone may not be sufficient to contribute to the observed patterns of mate choice in the Hutterites and to individual variation in odor preferences.

Alleles↗

PubMed2005

Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.

Limb girdle muscular dystrophy (LGMD) is very common in the Hutterite population of the North American Prairies. We have recently reported the homozygous c.1459G>A mutation in TRIM32 associated with LGMD2H. We have also identified Hutterite patients with LGMD2I, homozygous for the common c.826C>A mutation in FKRP. To date, all Hutterites with LGMD have been shown to be homozygous for either the TRIM32 or FKRP mutation. We now report a Hutterite family in which both parents and five sons were all found to be homozygous for the TRIM32 mutation. The father had slowly progressive proximal muscle weakness, whereas three sons and their mother, all currently asymptomatic, had normal physical examinations. The remaining two sons (7 and 10 years old), presented with mild decrease in stamina, had normal neuromuscular examinations and were found to be homozygous for the FKRP mutation in addition to the TRIM32 mutation. These two boys do not differ in age at or mode of presentation, physical findings, or serum CK levels compared to age-matched individuals affected with LGMD2I alone. This suggests that the effects of these two mutations are not acting synergistically at this time. It remains to be seen whether there will be signs of interaction between these two mutations as the patients get older.

Adult↗

PubMedDate not supplied

Declining fertility among North American Hutterites: the use of birth control within a Dariusleut colony.

Historically, population researchers considered the Hutterites the champions of high fertility, since they most closely approximated the human fertility potential. Yet contemporary researchers have found evidence of a decline in fertility and a shift from natural to controlled fertility behavior among the Hutterite population. Various reasons for these recent changes have been suggested, including the use of birth control. Using interview data from a Dariusleut colony, this is the first paper to document the presence and prevalence of birth control among the North American Hutterites. All interviewed women recognized the use of birth control and reported that female sterilization was the most commonly used method. I address how the various forms of birth control and the reasons for its use relate to the Hutterite ideology.

Adult↗

PubMed1989

Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren.

In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely.

Canada↗

PubMed1993

Determinants of peak flow rate among Hutterite farmers.

Observations from respiratory studies of over 1000 Hutterites and 200 control subjects indicated that the percent predicted peak flow rate values were 20% lower among Hutterites than control subjects. The purpose of this study was to determine if the decreased peak flow rate values among male Hutterites were a function of decreased airway patency or decreased respiratory muscle strength. Peak flow rate, muscle and lung function and the prevalence of respiratory symptomatology and disease were evaluated in 27 males from two Hutterite colonies. In one group almost all members consistently used masks while performing farming tasks, while 41% of members from the other colony used masks intermittently. Results suggest that peak flow rate values are decreased predominantly due to decreased airway patency associated with a higher prevalence of respiratory symptoms and disease and are not limited by respiratory muscle strength.

Adult↗

PubMed1992

Attitudes toward genetic testing of Amish, Mennonite, and Hutterite families with cystic fibrosis.

BACKGROUND: We had the unique opportunity to study families with cystic fibrosis (CF) from an interrelated Amish-Mennonite kindred and from an isolated Hutterite kindred. METHODS: While obtaining blood for DNA linkage analysis to help find the CF gene, we asked family members to answer a questionnaire about attitudes and feelings toward genetic testing. The questionnaire was also administered to families receiving care at the University of Rochester. After DNA-based CF carrier testing was developed, we asked the families whether they wanted to know the results. RESULTS: Each cultural group felt differently about many issues. Between 31% and 78% approved of CF-carrier testing and 14% to 78% approved of prenatal diagnosis. The majority (59%) of Hutterite parents and siblings were opposed to carriers marrying carriers and most (82%) of the CF families wanted to know the results of carrier testing. CONCLUSIONS: Cultural differences need to be understood before genetic services are offered. Also, most CF mutations and their clinical correlates (phenotypes) will need to be defined. There are as few as three CF mutations in the Hutterite population. It will be possible to offer them the option to choose accurate genetic counseling. It will be difficult to offer genetic services to other populations with more heterogeneous attitudes and many more identified and yet-to-be-identified CF mutations.

Abortion, Therapeutic↗

PubMed1985

Congenital contractures, edema, hyperkeratosis, and intrauterine growth retardation: a fatal syndrome in Hutterite and Mennonite kindreds.

We present clinical findings in infants from three kindreds (two Hutterite and one Mennonite) with an apparently unique, fatal disorder. The major manifestations consist of severe intrauterine growth retardation, congenital contractures, and tense skin which is easily eroded. The skin is tightly drawn over the face, giving an abnormal appearance consisting of a narrow, pinched nose, small mouth, limited jaw mobility, and ectropion (in one). One infant had first-degree hypospadias. Apart from this, there were no organ malformations and the infants did not have hydrops. Histologically, the skin showed hyperkeratosis. It is postulated that this is a tissue dysplasia and that all of the clinical effects are secondary. The disorder appears to be an autosomal recessive trait. The two Hutterite families are from different endogamous subdivisions. They are related as fourth cousins once-removed and fifth cousins in multiple ways through the six nearest common ancestors of all four parents. There are 25 founders (11 couples and three individuals) who are common ancestors. We computed the probability of joint descent of the four alleles in each pair of parents and in a sample of Alberta Hutterite couples, assuming that each of the common founders in turn was the original carrier. For an allele from one particular founder couple, there is a relatively greater probability of identity by descent for each pair of parents than on the average for other couples of the same endogamous subdivision.

Abnormalities, Multiple↗

PubMed1995

Prevalence of psychosis among the Hutterites: a reanalysis of the 1950-53 study.

Psychiatric case records from Eaton and Weil's 1950-53 study of the Hutterites were rediagnosed using DSM-III-R criteria. The results confirmed that the Hutterites have a very low prevalence of both schizophrenia (0.9 per 1000) and bipolar disorder (0.6 per 1000). Genetic and/or environmental explanations are both possible. Because of their unusual genetics and lifestyle, the Hutterites are an invaluable potential research resource.

Alberta↗

PubMed1987

Studies of cystic fibrosis in Hutterite families by using linked DNA probes.

Several multigenerational S-leut Hutterite families with cystic fibrosis (CF) were ascertained. Linkage studies with DNA marker loci MET and pJ3.11 (D7S8) were performed to determine whether (1) the CF gene in this inbred population is linked to DNA markers on chromosome 7, as it is in outbred populations of European origins, and (2) ancestral origin(s) of the CF gene could be determined. Our results indicate that the CF gene in Hutterite families segregates with chromosome 7 markers, identified by probes metH and pJ3.11. Thus, the CF mutation in Hutterites is likely to be either at the same locus as or at one closely linked to that reported in outbred populations. Heterozygous carriers could be distinguished from normal homozygous sibs of affected individuals. In the families studied, three different chromosome 7 haplotypes carried the CF mutation, raising the possibility that the CF gene may have been introduced into this population by as many as three different ancestors.

Chromosomes, Human, Pair 7↗

PubMed1994

Trends in cohort fertility of the Dariusleut Hutterite population.

A church book containing vital information on Dariusleut Hutterite families enabled us to trace the life course of individual women. We conducted a retrospective cohort study on the women born in the Dariusleut sect for the period 1901-1965, focusing on their marriage and reproductive histories. The subjects were grouped into 5-year birth cohorts from 1901-1905 to 1961-1965. The marital age-specific fertility rate (MASFR) increased from the 1901-1905 cohort to the 1926-1930 cohort and then began to decrease, particularly at the ages of 30-39 years. The initial increase in MASFR was not reflected directly in the cohort mean of the total number of children per woman because of a concurrent delay in age at marriage. Marriage delay, however, could not explain the drastic decrease, which started in the 1931-35 cohort, in the total number of children per woman; the decrease in MASFR at the ages of 30 years and older was considered a major reason for the recent changes in Hutterite fertility. The causes of the recent fertility decrease of Hutterites at higher ages remain to be investigated.

Adult↗

PubMed1997

Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci.

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders affecting primarily the shoulder and pelvic girdles. Autosomal dominant and recessive forms have been identified; 8 have been mapped and 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives with only mildly elevated CK levels were assigned an unknown phenotype to prevent their possible misclassification. Two-point linkage analysis of the disease locus against markers linked to 7 of the known LGMD loci and 3 other candidate genes yielded lod scores of < or = -2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD.

Adolescent↗

PubMed1985

Multiplicity of genetic polymorphisms of blood in the Schmiedeleut Hutterites.

Ninety-eight alleles in 38 polymorphisms of blood are identified in the Schmiedeleut Hutterites. The study was initiated because of the presence of Wda, an allele found almost exclusively in Hutterites. Eight of the other alleles also have an exceedingly low incidence in a random white population: r'' (.006), R2w (less than .001), LWb (less than .01), ESD*rare (less than .001), GPT*0 (.004), NP*4 (less than .001), GOT2*3 (.001), and C6*0 (.002). The occurrence of this many rare alleles in a population with an estimated maximum of 124 ancestral genomes was surprising but consistent with observations in other isolates. The degree of heterozygosity and large family size make the population ideal for genetic linkage studies.

Blood Group Antigens↗

PubMed1985

Muscular dystrophy in Saskatchewan Hutterites.

A slowly progressive form of muscular dystrophy was studied in a Dariusleut Hutterite kindred from a colony in west-central Saskatchewan. The disorder combines some characteristics of the dominantly inherited facio-scapulo-humeral and the recessively inherited limb-girdle types of muscular dystrophy. Intellect, vision, hearing, and sensations were normally preserved. Nerve conduction was also intact. The disorder reported herein resembles a type of muscular dystrophy we previously described in the Manitoba Schmiedeleut Hutterites [Shokeir and Kobrinsky, 1976]. This condition, which affects both sexes, appears to be genetic in origin and recessively inherited.

Consanguinity↗

PubMed1985

Screening for methylmalonic aciduria in Alberta: a voluntary program with particular significance for the Hutterite Brethren.

A selective, voluntary urine screening program has been established to facilitate detection and early treatment of infants with methylmalonic acidurias (MMA), a group of rare, potentially lethal, autosomal recessive disorders of organic acid metabolism. The laboratory methods have been modified for newborn infants so that urine specimens can be collected on filter paper in the diaper and tested by the thin-layer chromatography method. One Hutterite child was previously known to have methylmalonyl-coenzyme A (MMCoA) mutase deficiency (mut0) which is unresponsive to vitamin B12 but is responsive to diet and other therapeutic measures. No undiagnosed existing cases of MMA were identified by the voluntary screening program among 1,165 Hutterite infants and preschool children.

Alberta↗

PubMed1983

Patterns of cancer in geographic and endogamous subdivisions of the Hutterite Brethren of Canada.

The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar.

Canada↗

PubMed1995

Extended HLA profile of an inbred isolate: the Schmiedeleut Hutterites of South Dakota.

HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA and fertility. A total of 1,082 individuals, including 852 married adults representative of the reproductive population of this isolate, were characterized for five-locus HLA haplotypes. HLA-A1, A2, A3, and A24 accounted for 75% of observed HLA-A alleles and HLA-B27, B35, B51, and B62 accounted for 55% of observed HLA-B alleles. S-leut Hutterites are derived from 68 or fewer ancestors. However, only 48 ancestral HLA haplotypes were observed and nine of these accounted for over 52% of the observed haplotypes. Measures of two-locus linkage disequilibrium derived from these haplotypes indicated that one-third to half of the observed HLA-A/B, B/DR, and A/DR allele combinations exhibited highly statistically significant linkage disequilibrium. Allele and haplotype frequencies did not differ between males and females. Recombination rates of 0.004% and 0.005% between HLA-A and -C and between HLA-B and -DR, respectively, were observed. This HLA profile points out a paucity of HLA alleles and haplotypes in this population and marked linkage disequilibrium among the HLA alleles that are present.

Alleles↗

PubMed2001

Transmission/disequilibrium test analysis of total serum IgE levels in the Hutterite and Collaborative Study on the Genetics of Asthma data sets.

The Hutterite and Collaborative Study on the Genetics of Asthma data sets provided by Genetic Analysis Workshop 12 were analyzed using a regression-based transmission/disequilibrium test that assesses linkage between a marker locus and quantitative trait locus when allelic association is present, as proposed by George et al. [Am J Hum Genet 65:236-45, 1999]. Because the same marker set and analytical technique was used, the results from these data sets are amenable for comparison. Statistically significant results common to both data sets were found on chromosomes 1 and 3. A noteworthy result, significant at p < 10(-4), was detected on chromosome 18 in the Hutterites.

Adult↗