Genetic variability of HLA in the Dariusleut Hutterites. A comparative genetic analysis of the Hutterities, the Amish, and other selected Caucasian populations.

There are three endogamous subdivisions of the Hutterite population, a North American religious isolate. These individuals live on communal farms, and residence is strictly patrilocal. We report on the distributions of HLA-A and B alleles and haplotypes in 203 married women from one subdivision--the Dariusleut--in Alberta, Canada. We demonstrate that there is significant linkage disequilbrium among a large fraction of the distinct haplotypes in the Dariusleut Hutterite data; there is a restriction in the number of distinct haplotypes present in the Dariusleut; the Hutterites and the Old Order Amish (Lancaster County, Pennsylvania) are the most genetically distant pair of populations in an ensemble of 11 Caucasian populations; and, finally, the Old Order Amish and the Hutterites are approximately as distant from the Indiana Amish as they are from the eight other Caucasian populations, which are tightly clustered in the space of gene frequencies. These results are consistent with the fact that the Amish and the Hutterites are genetic isolates with small numbers of founders. Certain haplotypes show significant linkage disequilibrium in these as well as in other Caucasian samples. Thus, some of the linkage disequilibrium antedates the formation of these Anabaptist sects.     

Genetic structure of Mennonite populations of Kansas and Nebraska

We describe the gene frequency distributions for 29 different blood group, serum, and erythrocytic proteins for three Mennonite communities from Kansas and Nebraska and compare their gene frequencies with those of Amish, Hutterite, and Mennonite populations using the topological method of Harpending and Jenkins (1973). Subdivision of these communities into congregations reveals that the "fission-fusion'h model best characterizes the relationship between the genetic patterns and historical events. These Mennonite populations, although reproductively isolated at the turn of this century, are presently entering the mainstream of US rural culture.     

The age pattern of fecundability: an analysis of French Canadian and Hutterite birth histories

This paper analyzes the age pattern of effective fecundability from populations with no evidence of deliberate fertility control using a new convolution model of fecundability. The analysis is based on a sample of Hutterite birth histories from the mid-20th century, and birth histories of French Canadians from the 17th and 18th centuries. The main findings are as follows: 1) the level of effective fecundability is higher among the French Canadians compared to the Hutterites; 2) effective fecundability peaks at age 20 for the Hutterites, and in the early to mid-20s for the French Canadians; 3) Hutterite effective fecundability declines almost linearly from age 20 to 45, and French Canadian effective fecundability declines slowly from its peak to the early 30s, and more rapidly at older ages; and 4) the duration of postpartum amenorrhea is longer for the French Canadians than for the Hutterites. Because of the shorter periods of postpartum amenorrhea the Hutterites have about the same average number of children as the French Canadians, even though the French Canadians have higher effective fecundability.     

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.     

High fertility of Old Colony Mennonites in Mexico

Old Colony Mennonites in Mexico appear to demonstrate natural fertility, using no form of artificial birth control and apparently not attempting to limit family size. The resulting fertility is nearly as high as that of the Hutterites, although the Mennonites lack the communal economic system of the latter. Most Mennonites in Mexico migrated from Canada in the 1920s, and the largest single settlement, called the Manitoba Colony, is one of four in the state of Chihuahua. A 1967 partial census obtained data from 38% of the Mennonite households. Family size in the sample was close to that in a local survey taken in the same year. Available church records matched with census forms permitted verification of and corrections to 560 female reproductive histories. The median number of live births to women over age 45 years was 9.5, compared with 10.4 in the Hutterites. Age-specific marital fertility rates and birth intervals closely resembled those of the Hutterites.     

Inbreeding and reproductive parameters among Mennonites in Kansas

Abstract

The relationship between inbreeding and certain reproductive parameters was studied by analyzing the reproductive history questionnaires collected from 194 women who attended a research clinic in the Mennonite community of Goessel, Kansas, and for whom pedigrees were constructed from data at the Mennonite Historical Library and at the Alexanderwohl Church. Five reproductive parameters, age of menarche, age of menopause, length of reproductive span, number of children, and fetal wastage, were compared in inbred and noninbred women. There is no consistent evidence that absence of inbreeding or degree of inbreeding (F = 0.00024—0.0332) significantly affects these reproductive parameters in this sample of Mennonite women. If inbreeding does have an effect on these reproductive variables, it is too small to be detected in this sample.     

Inbreeding effects on fertility in humans: evidence for reproductive compensation.

The effects of inbreeding on prereproductive mortality have been demonstrated in many natural populations, including humans. However, little is known about the effects in inbred individuals who survive to adulthood. We have investigated the effects of inbreeding on fertility among inbred adult Hutterites and demonstrate significantly reduced fecundity among the most inbred Hutterite women, as evidenced by longer interbirth intervals (P=.024) and longer intervals to a recognized pregnancy (P=.010) but not by increased rates of fetal loss (P>.50). These data suggest the presence of recessive alleles that adversely affect fecundity among the population. In contrast, completed family sizes do not differ among the more and the less-inbred Hutterite women who were born after 1920, suggesting that reproductive compensation is occurring among the more-inbred and less-fecund women. This recent reproductive strategy would facilitate the maintenance of recessive alleles and contribute to an overall decline in fertility in the population.     

Decreased fecundability in Hutterite couples sharing HLA-DR.

To study the effects of parental HLA sharing on pregnancy outcome, we initiated population-based studies in the Hutterites. We previously reported longer intervals from marriage to each birth among couples sharing HLA, particularly HLA-DR. In the present report, we present the results of a prospective, 5-year study of fecundability and fetal loss rates in this population. Between April 1986 and April 1991, 154 pregnancies were observed in 104 couples. The median number of months of unprotected intercourse to a positive pregnancy test was significantly longer among couples sharing HLA-DR who stopped nursing prior to the first menses as compared with couples not sharing HLA-DR who stopped nursing prior to the first menses (5.1 vs. 2.0 mo, respectively; P = .016). Fetal loss rates were increased among couples sharing HLA-B as compared with couples not sharing HLA-B (.23 vs. .12, respectively; P = .041, adjusted for age, gravidity, and kinship). These data suggest that our earlier observations of increased birth interval lengths among Hutterite couples sharing HLA were predominantly due to longer intervals until a clinical pregnancy among couples sharing HLA-DR and, to a lesser degree, were due to increased fetal loss rates among couples sharing HLA-B.     

Towards a complete North American Anabaptist Genealogy II: analysis of inbreeding

We describe a large genealogy data base, which can be searched by computer, of 295,095 Amish and Mennonite individuals. The data base was constructed by merging our existing Anabaptist Genealogy Database 2.0 containing approximately 85,000 individuals with a genealogy file containing approximately 242,000 individuals, kindly provided by Mr. James Hostetler. The merging process corrected thousands of inconsistencies and eliminated hundreds of duplicate individuals. Geneticists have long been interested in Anabaptist populations because they are closed and have detailed written genealogies. The creation of an enlarged and unified data base affords the opportunity to examine inbreeding trends and correlates in these populations. We show the following results. The frequency of consanguineous marriages shows steady increase over time and reached approximately 85% for individuals born in 1940-1959. Among consanguineous marriages, the median kinship coefficient stayed stable in the 19th century, but rose from 0.0115 to 0.0151 in the 20th century. There are statistically significant associations (p < 0.0001) between inbreeding and family size and interbirth intervals in the 20th century. There is an association (p < 0.0005) between inbreeding and early death for individuals born in 1920-1959. However, this association reverses dramatically (p < 0.0005 in the opposite direction) for individuals born in 1960-1979. We tested for an association between inbreeding and being the mother of twins, but found none.     

HLA and mate choice in humans.

Evidence from studies in rodents suggests that mate selection is influenced by major-histocompatibility-complex haplotypes, with preferences for dissimilar partners. This study was initiated to determine whether avoidance of a mate with the same HLA haplotype as one's own might be occurring in the Hutterites, a North American reproductive isolate of European ancestry, notable for their large sibships, communal lifestyle, and limited number of five-locus HLA haplotypes (HLA-A, -B, -C, -DR, and -DQ). HLA haplotypes were known for 411 Hutterite couples. The number of couples expected to match for a haplotype was calculated in two ways: first, from population genotype frequencies, with account being taken of the nonrandom mating pattern with respect to colony lineages, and, second, from computer simulations using conservative founder assumptions and the exact genealogy of the 411 couples. We observed fewer matches for HLA haplotypes between spouses than expected (first method, P = .005; second method, P = .020-.067). Among couples who did match for a haplotype, the matched haplotype was inherited from the mother in 29 cases and from the father in 50 cases (P = .018). These results are consistent with the conclusion that Hutterite mate choice is influenced by HLA haplotypes, with an avoidance of spouses with haplotypes that are the same as one's own.     

Low twinning rate and seasonal effects on twinning in a fertile population,the Hutterites

This paper analyzes from the mid 18th century to 1987 the birth records of the Dariusleut, one of the three subgroups of the Hutterite population. The aim of this study is to describe several aspects of the twinning rate in a fertile population. The overall rate of twinning was 0.90%:103 twins among all 11492 maternities. The rate peaked at the 7th birth order and at the maternal age of 40 years and over. Until the mid 19th century when the Hutterites lived in Russia, the twinning rate was higher (1.5%), and it decreased during the migration period in the second half of the 19th century (0.7%). After the group had settled in the USA and Canada, the population maintained a twinning rate of 1.0% until 1965. After 1965 the rate decreased to 0.7%, partly due to a decline in fertility among women aged 30 years and over. There was a significant seasonal variation: the twinning rate decreased to 0.5% in May–July compared to 1.2% for the other three seasons during the years up to 1965 (P<0.01), while more recent mothers did not show such a seasonal variation. The incidence of twin births in this population seems to have been influenced by environmental factors, which would change their effect seasonally and secularly.     

Genetic homogeneity of cystic fibrosis.

We studied large Amish/Mennonite/Hutterite kindreds that segregate cystic fibrosis (CF) for linkage between CF and the polymorphic DNA markers pJ3.11 and 7C22 located on chromosome 7. These inbred pedigrees consist of more than 300 members including 30 affected individuals. In these families, linkage between the CF locus and the chromosome 21 marker D21S5 and between CF and the marker at the met oncogene locus on chromosome 7 had been previously indicated. We now report linkage between CF and pJ3.11 (Z = 4.92, theta = 0) and between CF and 7C22 (Z = 3.42, theta = 0). Therefore, CF segregates in these large pedigrees in a manner consistent with data from smaller outbred families with respect to the markers on chromosome 7 closest to CF. These data are consistent with locus homogeneity for the defect causing CF in the populations that have been examined to date.     

A comparison of sex ratio,birth periods and calf survival among Serengeti wildebeest sub‐populations,Tanzania

Although adaptation and environmental conditions can easily predict demographic variation in most savannah ungulates, no study on demographic consequences arising from natural and anthropogenic factors among Serengeti wildebeest (Connochaetes taurinus) sub‐populations in Tanzania has been carried out. Here, I report estimates of annual sex ratio, calf and yearling survival rate and birth seasonality between resident and migratory sub‐populations to explore demographic patterns arising from the different age and sex structure. The results indicate significantly higher female‐biased sex ratios in the resident and almost even sex ratios among individual migrants. The calf recruitment estimated as mother: offspring ratios indicate a more synchronous birth in the migrant than the resident sub‐population. Also, birth seasonality in the migratory sub‐population coincided with seasonal variability of rainfall and the timing of the birth peak was more variable in the migrants than the resident sub‐population. The migratory sub‐population had a higher annual proportional mean calf survival estimate (0.84) than that of the residents (0.44) probably due to higher mortality resulting from predation in the western corridor. However, the proportion of yearling survival estimates was much lower (0.31) in the migrants and relatively higher (0.39) in the residents. Different demographic outcomes resulting from environment, predation, movements and ecological factors including resource competition have conservation implications for the two sub‐populations.     

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.     

Historical sketch of Slovak Haban (Hutterite) population based on autosomal STR analysis

According to the Hutterite chronicles, the Habans arrived from Austrian Tyrol, Switzerland, and northernmost Italy and stayed in four regions of Slovakia (Soboti?te, Vel'ké Leváre, Moravsky Sv?ty Ján, Tren?ín). There are some communities in western Slovakia that retained their Haban cultural identity and still identify themselves as descendents of the Hutterite population with their own specific customs. Slovak Habans are typical founder population with significant social isolation for which high degree of inbreeding is typical. Present study investigated STR polymorphisms as a powerful genetic tool for population genetic studies. The aim was to perform a comparative, population genetic study based on 15 STR loci widely used in forensic genetics, of the Haban population, the Slovak majority population and the population of Tyrol. We analyzed allele frequencies and other statistical parameters in three selected populations in order to identify groups of specific ethnic origin and establish their genetic relationship. The data set included 110 unrelated Habans and 201 unrelated individuals from the Slovak majority population, as well as allelic frequencies for the population of Austrian Tyrol available in the literature. Population pairwise FST values used as a short term genetic distance between populations showed significant differentiation between the Habans and both reference populations (FST=0.0025 and 0.0042 for comparison with the Slovaks and Austrians, respectively; p<10(-3)). The Slovak Hutterites were demonstrated to be genetically distinct and more closely related to their geographic neighbors than to their historical ancestral population, which may be at least partially explained by gene flow between neighboring Haban and Slovak populations.     

Genetic analysis of HLA in the U.S. Schmiedenleut Hutterites.

The Hutterites are an Anabaptist population, highly inbred, with large family sizes and extensively documented pedigrees. As part of genetic-epidemiologic studies of the impact of HLA on fertility, HLA-A, -B, -C, -DR, and -DQ typing was performed on a total of 650 Schmiedenleut Hutterities in South Dakota. An extraordinary degree of homogeneity was found. HLA-A1, -A2, -A3, -A24, and -A26 accounted for 83%, HLA-B8, -B27, -B35, -B51, -Bw60, and -Bw62 for 75%, and HLA-DR1, -DR2, -DR3, and -DR4 for 66% of the antigens at the respective HLA-A, -B, and -DR loci. All Hutterites characterized for HLA were descendants of no more than 78 ancestors. However, family analysis identified only 45 unique HLA haplotypes thought to reflect the original gene pool. Eight haplotypes were particularly frequent, accounting for nearly 50% of all observed haplotypes; four of these were consistent with a European ancestry. Coefficients measuring linkage disequilibrium were computed from haplotypes identified by family analysis. Overall, HLA analysis portrayed the Schmiedenleut Hutterities as a homogeneous and unique population, with disequilibrium among particular alleles and a spectrum of common and uncommon European haplotypes.     

Maternal lineages and Alzheimer disease risk in the Old Order Amish

Old Order Amish, founded by a small number of Swiss immigrants, exist in culturally isolated communities across rural North America. The consequences of genetic isolation and inbreeding within this group are evident by increased frequencies of many monogenic diseases and several complex disorders. Conversely, the prevalence of Alzheimer disease (AD), the most common form of dementia, is lower in the Amish than in the general American population. Since mitochondrial dysfunction has been proposed as an underlying cause of AD and a specific haplogroup was found to affect AD susceptibility in Caucasians, we investigated whether inherited mitochondrial haplogroups affect risk of developing AD dementia in Ohio and Indiana Amish communities. Ninety-five independent matrilines were observed across six large pedigrees and three small pedigrees then classified into seven major European haplogroups. Haplogroup T is the most frequent haplogroup represented overall in these maternal lines (35.4%) while observed in only 10.6% in outbred American and European populations. Furthermore, haplogroups J and K are less frequent (1.0%) than in the outbred data set (9.4–11.2%). Affected case matrilines and unaffected control lines were chosen from pedigrees to test whether specific haplogroups and their defining SNPs confer risk of AD. We did not observe frequency differences between AD cases compared to controls overall or when stratified by sex. Therefore, we suggest that the genetic effect responsible for AD dementia in the affected Amish pedigrees is unlikely to be of mitochondrial origin and may be caused by nuclear genetic factors.     

Ancestral and recombinant 16-locus HLA haplotypes in the Hutterites

 Prior studies in the Schmiedeleut Hutterites of South Dakota have demonstrated associations between human leukocyte antigen (HLA) haplotype matching and fetal loss (Ober et al. 1992) and mate preferences (Ober et al. 1997), as well as deficiencies of homozygotes for HLA haplotypes (Kostyu et al. 1993). These studies were based on the serologically-defined five-locus HLA-A, -C, -B, -DR, -DQ haplotype. To further elucidate the effects of specific major histocompatibility (MHC) loci or regions on fetal loss and mate choice, we genotyped a sample of Hutterites for 14 MHC loci by DNA or biochemical methods. Typing for additional loci in the HLA-A to HLA-DPB1 region increased the number of recognized Hutterite MHC haplotypes to 67, and further localized the site of cross-over in 9 of 15 recombinant haplotypes. Hutterite MHC haplotype sequences are similar to those observed in outbred Caucasians, suggesting that the influence of HLA haplotypes on fetal loss and mating structure may be general. Received: 1 May 1998 / Revised: 2 December 1998     

Analysis of ethnic differences in perinatal statistics.

The 3996 mothers delivered at Dudley Road Hospital, Birmingham, in 1979 were analysed for their ethnic origins. Social classes IV and V predominated in all groups. A high proportion of Indian mothers fell into the low-risk group based on age and parity but had the highest stillbirth and perinatal mortality rates (15.1 and 27.5/1000 respectively) and infants of low mean birth weight (2986 g). Elderly and multiparous mothers were characteristic of the Pakistani and Bangladeshi groups. Young, primiparous mothers were more common among the West Indians and Europeans, in whom the stillbirth and perinatal mortality rates were low; infants in the European group had a mean birth weight higher than in any other group (3231 g). From these findings ethnic origin of the mother is apparently an important factor in perinatal mortality.     

Family resemblance for neuromuscular performance in a Kansas Mennonite community

Familial phenotypic resemblance for six quantitative neuromuscular performance traits is analyzed by path analysis using data from the Mennonite community of Goessel, Kansas. Of the six traits only one, dominant hand strength, shows no evidence of parent-offspring transmission (t2 = 0.001) and only one, trunk flexibility, shows evidence of a high degree of transmissibility (t2 = 0.662). The four remaining traits display low to moderate levels of transmissibility (t2 = 0.073 to t2 = 0.245). A substantial residual sibling resemblance due to shared environmental effects is seen for all six traits. It is suggested that the high heritabilities found for many of these traits by other methods result from the inability of these methods to account for the shared nongenetic effects.