Diversity of Autosomal Dominant Diseases in Populations of Russia

Results of 20-year studies on the diversity of autosomal dominant (AD) diseases are summarized. The studies were carried out in six regions of Russia: Kirov, Kostroma, and Bryansk oblasts; Krasnodar krai; and Adygea and Marii El republics. A total of 1.5 million subjects from 44 raions (districts) were studied. In the populations studied, 144 AD diseases were found; the total number of affected persons was 1723. The prevalence rate in the region where the disease was found and the average prevalence rate in the total population studied were calculated for each disease. Only 11 AD diseases had prevalence rates of 1 : 50 000 or higher. About half of AD diseases (64) had a very low prevalence rate (1 : 861 408). However, most cases (about 70% of the affected persons) were accounted for by more frequent diseases. Forty-six diseases exhibited local accumulation. The AD mutation rate was estimated by direct calculation. This rate was 0.542 × 10^–6per gamete per generation.     

A medico-genetic description of inhabitants of two regions of the Kransnodar Krai]

The spectrum and prevalence rate of hereditary pathology in Kanevskii and Bryukhovetskii raions (districts) of Krasnodar krai (territory) were analyzed. The total size of the studied population was 145,937. The prevalence rate of monogenic hereditary pathology was estimated. This value was 1.08 +/- 0.08, 0.72 +/- 0.07, and 0.20 +/- 0.06 per 1000 people for autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) recessive diseases, respectively. Forty-two AD (158 affected persons in 82 families), 32 AR (105 affected persons in 82 families), and 6 XL disease entities (13 affected persons in 8 families) were found. A slight genetic subdivision was found in the populations of Kanevskii and Bryukhovetskii raions. However, it was not found to affect the prevalence of hereditary pathology.     

Analysis of diversity of autosomal-recessive diseases in Russian populations]

The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected subjects was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1:50,000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1:877,483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (Fst) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (Fst) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift.     

Analysis of Diversity of Autosomal Recessive Diseases in Populations of Russia

The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1 : 50000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1 : 877483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (F _st) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (F _st) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift.     

Genetic Epidemiological Study of Three District Populations in Chuvashia

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.     

Genetic epidemiological study of populations in three regions of Chuvashia Republic

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.     

Prevalence of hereditary pathology in Altai Republic

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203 148 subjects, including 59 196 Altaians, 134 972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.     

Genetic epidemiological study of monogenic hereditary diseases in the Republic of Tatarstan: Population dynamic factors determining the differentiation of the load of hereditary diseases in five districts

A genetic epidemiological study has been performed in five districts of the Republic of Tatarstan, Russia: Arsky, Atninsky, Kukmorsky, Buinsky and Drozhzhanovsky raions. The total size of the population surveyed is 188397 people. Tatars accounted for 77.13% of the population analyzed (145466 people) and were represented by two main ethnic groups: Kazan Tatars and Mishars. The medical genetic study encompassed the total population of the districts, irrespective of ethnicity, and was carried out according to the standard protocol developed in the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics of the Russian Academy of Medical Sciences. After segregation analysis, the prevalence rates of the main types of monogenic hereditary disorders (MHDs), i.e., autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases, have been calculated for the total population of the five districts and for Tatars alone. The prevalence rates of AD, AR, and X-linked diseases considerably vary in different subpopulations. The largest difference in the MHD prevalence rate has been found between the rural and urban populations. The overall prevalence rate of MHDs was one patient per 293 urban residents and populations and one patient per 134 rural residents, with a wide variation between subpopulations, from 1: 83 people in the rural population of Atninsky raion to 1: 351 people in the town of Kukmor. Comparison of the MHD prevalence rate in Tatars with those in populations surveyed earlier has shown that the characteristics of the load of MHDs in the Tatar population are similar to those in some districts of the republics of Bashkortostan, Udmurtia, Mari El, and Chuvachia. In Russian populations of European Russia, the MHD prevalence rates are substantially lower. Correlation analysis has shown high (r = 0.5?C0.9) significant correlations between the local inbreeding (a), the im index, the random inbreeding (F _ST), and the AD and AR prevalence rates in the Tatar population. This analysis has demonstrated that genetic drift is the main population dynamic factor determining the MHD load in the Tatar population.     

Genetic and Epidemiologic Analysis of Hereditary Diseases of the Nervous System in the Cities of Volgograd and Volzhsky

A genetic epidemiological study of hereditary diseases of the nervous system (HDNS) was conducted in the cities of Volgograd and Volzhsky for the first time. In total, 1 323 500 individuals were examined including the populations of Volgograd and Volzhsky (1 012 800 and 310 700 persons, respectively). The prevalence of neurological diseases with autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive inheritance was estimated. These data were compared with the estimates previously obtained for different population of the Russian Federation. A decrease was found in general HDNS load in Volgograd and Volzhsky. The compared populations were shown to differ in a contribution of AD, AR, and X-linked recessive diseases into the HDNS load formation. The possible effect of population dynamics factors on the HDNS load structure is discussed.     

Genetic epidemiological study of Bashkortostan Republic: The effect of genetic structure of population on the load of monogenic hereditary diseases

Here we present the data obtained during medical genetic examination of the population of five districts of Bashkortostan Republic (Burzyanskii, Baimakskii, Abzelilovskii, Salavatskii, and Arkhangelskii) populated with 168050 persons including 135748 Bashkirs. The study involved all the population of the districts including each ethnic group and was conducted according to standard protocol developed in the Laboratory of Genetic Epidemiology, Medical Genetic Research Center, Russian Academy of Medical Sciences. Based on segregation analysis, the values of prevalence rates of the major types of Mendelian pathology (AD, AR, and X-linked diseases) was calculated in five regions of the Republic as well as for Bashkirs alone. Significant differences in the prevalence rates of AD and AR pathologies between individual districts, in particular upon division in rural and urban population, was observed. The prevalence rates comparison of monogenic hereditary pathology among Bashkirs compared to other previously examined populations have shown that the patterns of the hereditary disease load in the inspected districts of Bashkortostan were similar to that observed in the population of some districts in Udmurtia, Marii El and Chuvashiya. Russian European populations have shown significantly lower load of hereditary diseases. Correlation analysis of local inbreeding, endogamy and prevalence rates of AD and AR pathologies has shown that development of hereditary diseases load is significantly affected by gene drift.     

Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease

doi: 10.1111/j.1741‐2358.2011.00560.x
Indicators for root caries in Danish persons with recently diagnosed Alzheimer’s disease Objective: To identify indicators of root caries among persons with newly diagnosed Alzheimer’s disease (AD). Background: Few studies have investigated dental caries in older adults with AD. Previously we found that persons with AD had significantly more root caries compared to persons with dementia other than AD. Methods: Participants were recruited from two university hospital clinics in Copenhagen, Denmark. A team of neurologists/geriatricians carried out the diagnostic screening. The study included an interview, oral examination and medical records. Results: We evaluated potential indicators of root decay across subjects with 3+ decayed surfaces vs. <3 decayed surfaces. Variables associated with increased odds of root caries were age over 80 years, 2+ decayed coronal surfaces and 5+ filled root surfaces. Among the social variables, living with someone was associated with a nearly 70% reduction in the odds of having 3+ surfaces of untreated caries. Discussion: Root caries is highly prevalent among individuals with new AD and there is still a strong need for active assessment of and attention to oral problems in persons with AD. Our findings document that recently diagnosed AD cases with multiple coronal caries lesions are at elevated risk of having more root caries. Also persons 81+ years and those with multiple root fillings are more likely to have numerous untreated root lesions.     

Interaction between genes and environment in neurodegenerative diseases

Alzheimer's disease (AD) and Parkinson's disease (PD) are highly prevalent disorders that account for a large part of the global burden of neurodegenerative diseases. Most AD and PD cases occur sporadically and it is generally agreed that they could arise through interactions among genetic and environmental factors. Candidate genes involved in the metabolism of xenobiotics, neurodegeneration and functioning of dopaminergic neurons were found to be associated with PD. Some of these genes interact with environmental factors that could modify PD risk. Thus, we found that the inverse association between smoking and the risk of PD depended on a polymorphism of the iNOS (inducible NO synthase) gene. We also found that the cytochrome P450 2D6 gene could have a modifying effect on the risk of PD among persons exposed to pesticides. Both interactions have biological plausibility supported by laboratory studies and could contribute to better understand the aetiology of PD. A single susceptibility gene has been identified in sporadic AD. The epsilon4 allele of epsilon polymorphism of the apolipoprotein E gene (APOE) is strongly associated with AD, the risk of AD being multiplied by 5 in persons carrying two epsilon4 alleles. The mechanism of the association between APOE and AD is poorly understood. A few interactions between the epsilon polymorphism and possible risk factors for AD have been described. However, these interactions had no biological plausibility and were likely due to chance.     

Genetic and epidemiologic analysis of hereditary diseases of the nervous system in the cities of Volgograd and Volzhskiĭ

A genetic epidemiological study of hereditary diseases of the nervous system (HDNS) was conducted in the cities of Volgograd and Volzhsky for the first time. In total, 1 323 500 individuals were examined including the populations of Volgograd and Volzhsky (1 012 800 and 310 700 persons, respectively). The prevalence of neurological diseases with autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive inheritance was estimated. These data were compared with the estimates previously obtained for different population of the Russian Federation. A decrease was found in general HDNS load in Volgograd and Volzhsky. The compared populations were shown to differ in a contribution of AD, AR, and X-linked recessive diseases into the HDNS load formation. The possible effect of population dynamics factors on the HDNS load structure is discussed.     

甘肃临潭磨沟墓地人骨的牙齿健康状况

本文通过甘肃临潭磨沟齐家文化墓地出土的262例人骨标本的牙病情况尤其是龋病、牙周病、根尖周病以及牙结石情况的统计与分析,得知磨沟墓地古代居民牙齿疾病的基本情况:1)牙病的罹患率性别差异显著,女性龋病和根尖周病的罹患率高于男性,而在牙周病和牙结石的出现率上则是男性高于女性;2)牙病的罹患率随着年龄增长而增高;3)龋病、牙周病及根尖周病多发于臼齿,牙结石多发于门齿;4)重度磨耗牙齿多发牙周病及根尖周病;5)牙病罹患率不仅受到性别、年龄、牙位以及齿冠磨耗程度的影响,而且与磨沟组古代居民农业种植食物和采集食物并重的食物结构有关。     

DISEASES OF THE HEART IN A WORKING POPULATION—A Study of Morbidity and Mortality in Relation to Cardiac Status and Nature of Job

A sample consisting of 2,252 persons among 20,199 Los Angeles civil service employees was observed for the occurrence of heart disease. The first examination measured the prevalence. Based upon the diagnosis of 165 cases of heart disease, the prevalence was 73 per 1,000 persons examined.Two reexaminations, at intervals of 12 to 18 months, of persons with normal heart on the first examination were carried out and 52 additional cases were diagnosed. There were also 13 deaths of heart disease in persons first diagnosed as having normal heart, making a total of 65 “new” cases (36.6 per 1,000) during the 30-month period of observation. An annual estimated heart disease incidence of 15 per 1,000 appears reasonable.Based on 89 deaths, the cardiovascular disease death rate was 11 per 1,000 among persons entering the study with normal heart, and 133 per 1,000 persons diagnosed as having heart disease at entry. The ratio of newly diagnosed cases to deaths of heart disease was 4 to 1.Among men diagnosed as having normal heart there was little difference in death rates whether their jobs were physically strenuous or sedentary. Among the men with heart disease, however, the highest death rates are observed among those employed at sedentary jobs and at light exertion. This may, of course, be an indication of the employee''s selection of the job rather than the effect of inactivity. The relative usefulness of minifilm x-ray, electrocardiograms and questioning as to history were considered.     

Influence of age and sex on levels of anti-oxidized LDL antibodies and anti-LDL immune complexes in the general population

Most studies of antibodies to oxidized LDL have been undertaken in patients with different diseases and cardiovascular risk factors. However, very few studies have researched the distribution and determining factors of antibodies to oxidized LDL in the general population. A total of 1,354 persons (817 females and 537 males) aged 5-65 years were included in this study. They were selected randomly from the population census of Málaga, in southern Spain. The females had lower levels of total cholesterol and triglycerides and higher levels of HDL-cholesterol and a very significant increase (P < 0.0001) in levels of anti-oxidized LDL [low density lipoprotein modified by malondialdehyde (MDA-LDL)] antibodies but no difference in levels of immune complexes consisting of LDL and IgG antibodies (anti-LDL immune complex). Younger persons (16-35 years) had higher levels of anti-oxidized LDL (MDA-LDL) antibodies than persons older than 35 years (P = 0.05). Levels of immune complexes were significantly higher (P = 0.05) in persons aged 5-15 years than in persons older than 40 years. A very weak association was found between levels of anti-oxidized LDL (MDA-LDL) antibodies and anti-LDL immune complexes. The higher prevalence of anti-oxidized LDL (MDA-LDL) antibodies in females and young persons is in agreement with studies that found an inverse association between atherosclerosis and the level of these antibodies.     

Incidence of congenital heart disease in Hungary.

A survey was planned for establishing the point prevalence at birth of congenital heart disease and for assessing at the same time the efficacy of a screening for such anomalies. This model included: (1) exact determination of the population under survey; (2) approximately complete ascertainment of all persons in the population studied; (3) identical principles of cardiologic screening; (4) application of modern cardiologic diagnostic methods, and (5) a sample of over 2,000 persons. 23 cases of congenital heart diseases were found among 2,259 children born 1963 in a defined Hungarian territory. This means a point prevalence of 10.2+/-2.1% live births. (An additional 6 doubtful cases were not taken into account.) From the 12 cases diagnosed in vivo, 10 were detected by the screening.     

Epidemiology of fetal alcohol syndrome among American Indians of the southwest

Abstract

The epidemiological features of Fetal Alcohol Syndrome (FAS) were examined among American Indians in the southwestern United States. All FAS suspects were screened in specific populations of Navajo, Pueblo, and Plains culture tribes. A total of 115 alcohol‐affected children were identified. The incidence of FAS was found to be highly variable from one cultural group to the next, ranging from 1.3 per 1,000 births (1/749) for the Navajo to 10.3 (1/97) for the Plains. The pattern of age‐specific prevalence indicates an increase over the past fifteen years. The overall rate of mothers who have produced fetal alcohol children was 6.1 per 1,000 women of childbearing age with a range of 4 to 33 per 1,000. These maternal prevalence rates were important for the accurate prediction of public health risk because 25 per cent of all mothers who had produced one affected child had also produced others. The average per mother was 1.3 alcohol‐affected children. Other findings indicate that the mothers of these children led highly disruptive and chaotic lives and were frequently isolated from mainstream social activities. In general, the gross social and cultural patterns of the tribes studied can readily explain the variation in incidence of FAS.     

Diseases of the heart in a working population; a study of morbidity and mortality in relation to cardiac status and nature of job

A sample consisting of 2,252 persons among 20,199 Los Angeles civil service employees was observed for the occurrence of heart disease. The first examination measured the prevalence. Based upon the diagnosis of 165 cases of heart disease, the prevalence was 73 per 1,000 persons examined. Two reexaminations, at intervals of 12 to 18 months, of persons with normal heart on the first examination were carried out and 52 additional cases were diagnosed. There were also 13 deaths of heart disease in persons first diagnosed as having normal heart, making a total of 65 "new" cases (36.6 per 1,000) during the 30-month period of observation. An annual estimated heart disease incidence of 15 per 1,000 appears reasonable. Based on 89 deaths, the cardiovascular disease death rate was 11 per 1,000 among persons entering the study with normal heart, and 133 per 1,000 persons diagnosed as having heart disease at entry. The ratio of newly diagnosed cases to deaths of heart disease was 4 to 1.Among men diagnosed as having normal heart there was little difference in death rates whether their jobs were physically strenuous or sedentary. Among the men with heart disease, however, the highest death rates are observed among those employed at sedentary jobs and at light exertion. This may, of course, be an indication of the employee's selection of the job rather than the effect of inactivity. The relative usefulness of minifilm x-ray, electrocardiograms and questioning as to history were considered.     

Prevalence of Hereditary Pathology in Altai Republic

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203148 subjects, including 59196 Altaians, 134972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.