Diversity and Prevalence of Hereditary Diseases among Nogais of the Karachay-Cherkess Republic

The diversity and prevalence of hereditary diseases (HDs) among Nogais of the Karachay-Cherkess Republic (KChR) are described. The size of the surveyed KChR population was 387231 individuals, including 3.81% Nogais (14741 individuals). We revealed 36 nosological forms of HDs (110 patients from 81 families): 22 with autosomal dominant (AD) inheritance, 10 with autosomal recessive (AR) inheritance, and 4 with X-linked inheritance. The prevalence of HDs in Nogais was 1: 134. The features of HD diversity in Nogais were determined in comparison with the previously surveyed populations of Russia. The accumulation of Ehlers–Danlos syndrome (1: 388), AD amelogenesis imperfecta (1: 3685), AD ichthyosis (1: 4914), AR nonsyndromic mental retardation (1: 1340), AR Gilbert syndrome (1: 4914), and X-linked inherited deficit of glucose-6-dehydrogenase (1: 1774 males) was established. The analysis of heterozygous carriage of mutations “major” for Russia in the genes of the four following AR diseases in 118 unrelated clinically healthy Nogais (236 analyzed chromosomes) was performed: cystic fibrosis (13 mutations in the CFTR gene: CFTRdele2,3 (21 kb), F508del, I507del, 1677delTA, 2184insA, 2143delT, 2183AA>G, 2184delA, 394delTT, 3821delT, L138ins, E92K, W1282X); phenylketonuria (six frequent mutations in the PAH gene: R261X, R408W, R413P, F331S, P211T, P211L); nonsyndromic sensorineural hearing loss (35delG mutation in the GJB2 gene); and Gilbert syndrome (an increase in the number of TA repeats in the UGT1A1 gene). Allelic specificity for all studied genes in the Nogai people was revealed.     

Medical Genetic Study of Hereditary Diseases in Abazins of the Karachay-Cherkess Republic

This paper estimates the load and nosological spectrum of monogenic hereditary diseases (HDs) in Abazins of the Karachay-Cherkess Republic (KChR), identified in Cherkessk and ten districts, Abazinsky, Ust-Dzhegutinsky, Malokarachaevsky, Karachaevsky, Prikubansky, Khabezsky, Nogaysky, Adyge-Khablsky, Urupsky, and Zelenchuksky. The number of the investigated population was 387231 individuals (including 33264 Abazins). We detected 153 patients from 105 families with 45 nosological forms of HDs: 83 patients from 50 families with 23 AD diseases, 47 patients from 42 families with 15 AR diseases, and 23 patients from 13 families with 7 X-linked diseases. The total load of HDs in Abazins was 1: 218 individuals (in the rural population 1: 162, in the urban population 1: 305). Frequent and rare nosological forms of HDs and the accumulation of certain diseases in Abazins in comparison with the previously surveyed populations of Russia were determined. On the basis of the prevalence of AD and AR hereditary diseases, a principal component analysis was carried out, which determined the genogeographical position of Abazins among nine ethnic groups (13 populations) of Russian Federation: six Russian regions, Bashkirs of the Bashkortostan, Tatars of the Tatarstan, Chuvashes of the Chuvashia, Maris of the Mari El, Udmurts of the Udmurtia, Adygeans of the Adygea, and Circassians and Abazins of the KChR.     

Hereditary Disorders in Circassians of the Karachay-Cherkess Republic

The paper aims to review the diversity of monogenic hereditary disorders (MHD) in the Circassians of the Karachay-Cherkess Republic (KCR). In total, 50817 Circassians were investigated. The populations of eight districts (Ust-Dzhegutinsky, Karachayevsky, Malokarachayevsky, Prikubansky, Khabezsky, Abazinsky, Nogaysky, and Adyge-Khablsky) and of the city of Cherkessk were studied. Two hundred fifty patients from 167 families were registered. The prevalence of MHD in Circassians happens to be 1: 214. The nosological spectrum of MHD in Circassians includes 70 disorders: 34 with autosomal dominant, 25 with autosomal recessive, and 11 with X-linked inheritance patterns. Confirmatory DNA diagnostics was performed in 56 patients. Accumulation of particular diseases in the Circassian population was revealed in comparison with the previously surveyed ethnic groups/populations of Russia. The cluster analysis was performed on the basis of the prevalence of AD and AR disorders and determined the genogeographic position of the Circassians among eight ethnic groups of Russia (13 populations in total). The total size of the surveyed populations was over 3.5 million people: six Russian regions, Tatars of the Tatarstan, Bashkirs of the Bashkortostan, Chuvashs of the Chuvash Republic, Maris of the Mari El Republic, Udmurts of the Udmurt Republic, Adygeans of the Republic of Adygea, and Circassians of the Karachay-Cherkess Republic. The general pattern for AD and AR diseases was similar: six Russian populations group within a single cluster, being remote from people of the Volga-Ural region and the North Caucasus (Adyghe: Adygeans and Circassians).     

Russians of the Karachay-Cherkess Republic: Population Genetic Portrait

To describe the population-genetic structure of the Russian population of Karachay-Cherkessia, the database of Compulsory Medical Insurance and marriage records for 1990–2000 were used. The Russian population is characterized by a low birth rate, low endogamy, low inbreeding, and a high level of miscegenation.     

Study of the Role of the Main Factors of Population Dynamics in the Mechanism of Differentiation and Formation of Diversity and Genetic Load of Hereditary Diseases in Subpopulations of the Karachay-Cherkess Republic

Russian Journal of Genetics - The generalized results of the genetic and epidemiological study of the genetic structure of various ethnic groups of the Karachay-Cherkess Republic (KChR) through...     

The Load of Hereditary Diseases in the Population of Republic of Sakha (Yakutia)

Summarized data of medical genetic survey of the population of Republic of Sakha (Yakutia) are presented. The number of the population examined constituted 1 000 700 individuals (including 424 500 of urban and 576 200 of rural population, respectively). Regarding the ethnicity, 33 regions of the Republic examined were at most inhabited by Yakuts (36%) and Russians (55%). A total of 400 families (606 patients) with autosomal dominant, 274 families (369 patients) with autosomal recessive, and 42 families (53 patients) with X-linked pathologies were detected. The segregation analysis performed showed good correlation with the expected type of inheritance for both dominant and recessive diseases. The prevalence rate of monogenic hereditary diseases for rural and urban populations, as well as for solely Yakuts, was calculated. It was shown that weighted average prevalence of dominant (0.68; 1.44) and recessive (0.43; 0.86) disorders in Yakuts was two times higher than in total population examined.     

Hereditary Diseases of Nervous System in the Population of Vladimir Oblast

The first population genetic study of hereditary disorders of the nervous system (HDNS) in Vladimir oblast was carried out. A total of 1622900 subjects, including 1306200 from the urban and 316700 from the rural population, were tested. The population examined was characterized by virtually homogenous ethnic structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in Vladimir oblast corresponded to the average prevalence for other Russian populations. Substantial differences between urban and rural populations in respect of the population load of HDNS and its nosological structure were not observed. A total of 22 nosological forms of HDNS were revealed, including thirteen autosomal dominant (193 families with 272 affected individuals), seven autosomal recessive (59 families with 66 affected individuals), and two X-linked (15 families with 17 affected individuals) diseases. The composition of the HDNS spectrum nucleus in Vladimir oblast displayed a number of differences from that in the majority of other populations examined. The HDNS in different regions of the area tested were characterized by different prevalence and spectrum. The data obtained may constitute a basis for regional registration of HDNS in Vladimir oblast.     

Investigations on the Occurrence of Hereditary Diseases in the Danish Cattle Population 1989-1991

The methods of the Danish Bovine Genetic Disease Programme are outlined, and the results obtained during the first 3 years in function are described. The most common disease reported was spinal muscular atrophy in calves of the Red Danish Dairy breed with 312 reports. Necropsy was performed on 162 cases, and spinal muscular atrophy was diagnosed in 82 of these. Bovine progressive degenerative mye-loencephalopathy, rectovaginal constriction, syndrome of arthrogryposis and palatoschisis, hereditary chondrodysplasia (2 different types), syndactylism, epitheliogenesis imperfecta, and osteogenesis imperfecta was diagnosed with 1 case each. Lethal trait A46 was diagnosed in 4 calves. Some of these diseases have not previously been described in Denmark, and epitheliogenesis imperfecta was for the first time diagnosed in the Hereford breed. Chromosome translocation 1/29 was detected in the Blonde d’Aquitaine (BAQ), Limousine, and Red Danish Dairy breed. The aberration occurred frequently in BAQ. Furthermore, a complex chromosome translocation t(l;8;9)(q45;ql3;q26) was detected in the Red Danish Dairy breed.     

遗传性肾炎的遗传学研究进展

遗传性肾炎(hereditary nephritis,HN)是一组与遗传有关,主要累及肾小球的肾脏疾病,常伴有其它器官的损伤.HN呈家族聚集性,可表现为常染色体显性遗传、常染色体隐性遗传和X连锁遗传,有些家系还表现为非孟德尔遗传和线粒体遗传.对HN主要疾病的临床表型、遗传学和动物模型的总结和对HN疾病的深入研究有可能找到疾病的致病突变,以及更好地了解疾病的分子机制.     

传染性疾病的遗传易感性

传染性疾病是威胁人类健康的主要疾病类型之一。传染病的发生、发展是致病微生物、宿主的遗传因素与环境相互作用的结果。大量以单核苷酸多态性（SNP）为遗传标记,基于家系或无关群体的连锁和关联分析,已绘制出传染性疾病易感性的基因图谱。目前易感性的研究主要集中在疟疾、获得性免疫缺陷综合征、乙肝和严重急性呼吸系统综合征等传染性疾病。     

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.     

Antiretroviral Treatment Program Retention among HIV-Infected Children in the Democratic Republic of Congo

Background

Retaining patients with HIV infection in care is still a major challenge in sub- Saharan Africa, particularly in the Democratic Republic of Congo (DRC) where the antiretroviral treatment (ART) coverage is low. Monitoring retention is an important tool for evaluating the quality of care.

Methods and Findings

A review of medical records of HIV -infected children was performed in three health facilities in the DRC: the Amo-Congo Health center, the Monkole Clinic in Kinshasa, and the HEAL Africa Clinic in Goma. Medical records of 720 children were included. Kaplan Meier curves were constructed with the probability of retention at 6 months, 1 year, 2 years and 3 years. Retention rates were: 88.2% (95% CI: 85.1%–90.8%) at 6 months; 85% (95% CI: 81.5%–87.6%) at one year; 79.4% (95%CI: 75.5%–82.8%) at two years and 74.7% (95% CI: 70.5%–78.5%) at 3 years. The retention varied across study sites: 88.2%, 66.6% and 92.5% at 6 months; 84%, 59% and 90% at 12 months and 75.7%, 56.3% and 85.8% at 24 months respectively for Amo-Congo/Kasavubu, Monkole facility and HEAL Africa. After multivariable Cox regression four variables remained independently associated with attrition: study site, CD4 cell count <350 cells/µL, children younger than 2 years and children whose caregivers were member of an independent church.

Conclusions

Attrition remains a challenge for pediatric HIV positive patients in ART programs in DRC. In addition, the low coverage of pediatric treatment exacerbates the situation of pediatric HIV/AIDS.     

遗传性耳聋的分子遗传学研究进展

遗传性耳聋是指由基因或染色体异常所致的感音神经性聋。它可分为遗传性的综合征性耳聋 (ｓｙｎｄｒｏｍｉｃｈｅａｒｉｎｇｉｍｐａｉｒｍｅｎｔ,ＳＨＩ)和非综合征性耳聋 (ｎｏｎｓｙｎｄｒｏｍｉｃｈｅａｒｉｎｇｉｍ ｐａｉｒｍｅｎｔ,ＮＳＨＩ)。综合征性耳聋指耳聋只是构成全身多处临床症状之一的遗传综合征 ,而非综合征耳聋是指以听力损失为单一症状的遗传性疾病。耳聋的病因复杂 ,在发达国家 ,6 0 %的耳聋由遗传缺陷引起[1] 。新生儿中听力障碍群体发病率约为 1 /1 0 0 0 ,其中一半是遗传因素所致。随着分子遗传学技术在耳聋研究中…     

Population Genetics of Gene Function

This paper shows that differentiating the lifetimes of two phenotypes independently from their fertility can lead to a qualitative change in the equilibrium of a population: since survival and reproduction are distinct functional aspects of an organism, this observation contributes to extend the population-genetical characterisation of biological function. To support this statement a mathematical relation is derived to link the lifetime ratio T ₁/T ₂, which parameterizes the different survival ability of two phenotypes, with population variables that quantify the amount of neutral variation underlying a population’s phenotypic distribution.