[Molecular genetics in diagnosis of Coats disease: combination of oligogenic variants associated with different forms of hereditary retinal dystrophy]. / Molekulyarno-geneticheskie nakhodki pri diagnostike bolezni Koatsa: sochetanie oligolokusnykh izmenenii, svyazannykh s raznymi nozologicheskimi formami nasledstvennoi retinopatii.

Coats disease (OMIM 300216) is a form of hereditary retinal dystrophy, which occurs due to congenital abnormality of retinal vessels and features unilateral exudative vitreoretinopathy. Coats disease mostly occurs sporadically; its genetic cause is still undetermined. Molecular genetic research including whole exome sequencing by the NGS method was used to define a genetic cause of the observed phenotype. Two heterozygous variants in different genomic loci associated with other forms of hereditary retinal dystrophy were detected, a rare variant in the HMCN1 gene c.9571C>T, p.(Arg3191Cys), and a known pathogenic variant in the NPHP4 gene c.2930C>T, p.(Thr977Met). The HMCN1 gene is responsible for dominant age-related macular degeneration (OMIM 603075), pathogenic variants in the NPHP4 gene cause recessive Senior-Løken syndrome 4 (OMIM 266900). These genes encode the proteins that are involved in the regulation of integrity of the blood-retinal barrier in the vascular endothelium (NPHP4) and retinal pigment epithelium (HMCN1). The identified mutation in the NPHP4 gene could lead to decreased function of the NPHP4 protein and contribute to the development of retinal degeneration, potentially of oligogenic nature.

[Gyrate atrophy of the choroid and retina with ornithinemia and foveoschisis (clinical observation)]. / Atrofiya girate khorioidei i setchatki s ornitinemiei i foveoshizisom (klinicheskoe nablyudenie).

Gyrate chorioretinal atrophy (GCA) is a rare hereditary disease with certain complications; one extremely rare complication of GCA is foveoschisis. For the first time in Russian ophthalmology, a 10-year-old female child has been described to have genetically verified GCA associated with the OAT gene in combination with ornithinemia and foveoschisis. The diagnosis was made on the basis of fundus examination, perimetry data, autofluorescence, optical coherence tomography, fluorescence angiography, electroretinography, mass spectrometry with confirmation by molecular genetic research. The presented clinical case illustrates the need for an interdisciplinary approach to the diagnosis of GCA with diagnostic algorithm involving various examination methods and doctors of different specialties.

Genetic Landscape of Nephropathic Cystinosis in Russian Children.

Nephropathic cystinosis is a rare autosomal recessive disorder characterized by amino acid cystine accumulation and caused by biallelic mutations in the CTNS gene. The analysis methods are as follows: tandem mass spectrometry to determine the cystine concentration in polymorphonuclear blood leukocytes, Sanger sequencing for the entire coding sequence and flanking intron regions of the CTNS gene, multiplex PCR to detect a common mutation-a 57 kb deletion, and multiplex ligation-dependent probe amplification to analyze the number of exon copies in the CTNS gene. Haplotype analysis of chromosomes with major mutations was carried out using microsatellite markers D17S831, D17S1798, D17S829, D17S1828, and D17S1876. In this study, we provide clinical, biochemical, and molecular genetic characteristics of 40 Russian patients with mutations in the CTNS gene, among whom 30 patients were selected from a high-risk group of 85 people as a result of selective screening, which was carried out through cystine concentration measurement in polymorphonuclear blood leukocytes. The most common pathogenic variant, as in most described studies to date, was the 57 kb deletion, which represented 25% of all affected alleles. Previously non-described variants represented 22.5% of alleles. The founder effect in the Karachay and Chechen ethnic groups was shown for the following major variants: c.1015G > A and c.518A > G.

[The intermediate outcomes of delegation of obligations of medicinal support of patients with rare diseases to the Federal level in 2019-2020].

Lately, in case of a number of life-threatening and chronic progressive rare (orphan) diseases, resulting in decreasing of life expectancy of citizens or their disability, the powers to support patients with medications were transferred from regional to federal level. Among these diseases are hemolytic uremic syndrome, mucopolysaccharidose type I, II, VI, juvenile arthritis with systemic onset, unspecified aplastic anemia, hereditary deficiency of factors II (fibrinogen), VII (labile), X (Stuart-Prauer). The article considers data concerning hemolytic uremic syndrome, mucopolysaccharidosis type I, II, VI, juvenile arthritis with systemic onset - the diseases for which medication support provision was transferred to Federal level in the first place and for which at the time of preparation of the article there were sufficient data to analyze.

[The specialized medical care of children with rare diseases].

The article presents the results of analysis of specialized medical care of children with life threatening and chronic progressive rare (orphan) diseases resulting in life span shortening or disability. The possibility of medication support of children with rare diseases. The development of patient routing system considering characteristics of particular disease and possibilities of the subjects of the Russian Federation is one of most important directions of enhancement of needed medical care support.

[Analysis of associations of undifferentiated connective tissue dysplasia with the development of primary open-angle glaucoma. Clinical and genetic aspects]. / Analiz assotsiatsii nedifferentsirovannoi displazii soedinitel'noi tkani s razvitiem pervichnoi otkrytougol'noi glaukomy. Kliniko-geneticheskie aspekty.

Mutations and polymorphisms of the genes whose products are involved in the formation of extracellular matrix components can lead to the development of specific changes in the connective tissue of the eye in primary open-angle glaucoma (POAG). Understanding the nature of connective tissue pathology and its manifestations at the system level contributes to the development of specific markers of early detection and a personalized approach to the prevention and treatment of POAG. PURPOSE: To study the associations between systemic manifestations of undifferentiated connective tissue dysplasia (uCTD) and the development of POAG based on clinical and molecular genetic studies. MATERIAL AND METHODS: The observational study was conducted in the period from 2008 to 2021 (12 full years) and included retrospective data analysis of up to 15 years. The study involved 60 people with «suspected glaucoma¼ diagnosis and burdened heredity, who were divided into groups according to the severity of phenotypic signs of uCTD (on the T.I. Kadurina scale), as well as 15 people with «glaucoma¼ diagnosis whose morphological and immunohistochemical studies of the sclera were analyzed retrospectively. The comparison group consisted of 64 relatively healthy individuals. All patients underwent clinical-anamnestic, molecular-genetic, standard and special ophthalmological studies. RESULTS: Significant associations were revealed between the development of POAG, and the presence of clinical and phenotypic manifestations of uCTD, carriage of the GT genotype and the T allele of the rs8136803 (TIMP3) polymorphism, the AG genotype and the A allele of the rs652438 polymorphism (MMP12), the GA genotype and the A allele of the rs3825942 polymorphism (LOXL1). CONCLUSION: The specific features of preclinical morphofunctional changes and glaucoma progression can be determined by a hereditary predisposition to the pathology of the connective tissue of the eye. Testing of clinical-phenotypic and molecular-genetic signs of uCTD in patients with suspected glaucoma is promising in preclinical diagnosis, prognosis, and personalized approach to prevention and treatment.

[The normative legal regulation of medical care support of rare (orphan) diseases in adult population of The Russian Federation].

The article considers the results of legal regulation analysis of medical care support including medication maintenance of adult patients suffering from rare diseases exemplified by life-threatened and chronic progressed rare (orphan) diseases resulting in life expectancy decrease and or disability ("List-24"). MATERIALS AND METHODS: Law database was analyzed in terms of current orders of medical care provision, standards of medical care, and clinical guidelines for rare diseases from "List-24" regarding to adult patients. RESULTS: It is concluded that there are no determined rules of medical care provision to adult population in case of rare diseases from "List-24". There are standards of medical care on 6 rare diseases (25% of total diseases amount) from this list for adult patients. However, based on content analysis data of approved standards it was established that there are only 3 from 11 standards (27.28%) for primary medical care support, 4 standards (33.34%) for medical care provision in planned condition, and only 1 standard (9.09%) had appropriate legal basis for its development (clinical guidelines availability). Nevertheless, there is negative prognosis for this the only standard due to legal necessity of all clinical guidelines revision till the end of 2021. CONCLUSION: Revision and creation of clinical guidelines and standards of medical care afterwards are needed for adult patients treatment with rare diseases from "List-24". The conclusion was made in terms of medical care standardization improvement for adult patients suffering from rare diseases from "List-24" based on its alignment with current legal regulation.

[The cost of specialized medical care of children under spinal muscular atrophy in Moscow].

The spinal muscular atrophy is neuromuscular disease caused by mutations in SMN1 gene. The clinical picture of disease is characterized by progressive muscular weakness and atrophy associated with degeneration of spine, and in severe cases by affection of motor neurons of lower bulbar cells. The spinal muscular atrophy progressing course resulting in disability and infant mortality. Actually, specific treatment is at the stage of clinical trials. However, patients are needed in permanent symptomatic arresting of manifestations and pathogenetic treatment preventing development of disease. The article presents calculations of direct medical costs for treatment in pediatric patients (0-17 years old) in Moscow with the main types of spinal muscular atrophy. It is established that the cost of specialized medical care of children with spinal muscular atrophy per single under age patient in Moscow consisted 7,131,185.84 rubles annually, including primary diagnostic, treatment and rehabilitation and medicinal treatment. In total, according to data for 2020 in Moscow, where number of children patients is 144, the cost of specialized medical care of children with spinal muscular atrophy is estimated as 1,024,580,269.16 rubles. At that, data takes into account only direct medical costs for out-patient and in-patient care of children with spinal muscular atrophy, excluding number of exacerbations of disease. Taking into account average numbers of hospitalizations per year because of illness, the cost of in-patient care of single child amounts to 7,844,304.42 rubles annually and 1,127,018,732.08 rubles for all children with spinal muscular atrophy in Moscow (according data of 2020).

[Fundus albipunctatus with mutations in the RDH5 gene (clinical case)]. / Belotochechnoe glaznoe dno (fundus albipunctatus) s mutatsiyami v gene RDH5 (klinicheskoe nablyudenie).

The article describes a clinical case of a 14-year old patient with RDH5 mutations (OMIM *601617) in patient with fundus albipunctatus (OMIM #136880) and characteristic biomarkers of this disease with previously described pathogenic variant of nucleotic sequence in exon 3 of the RDH5 gene (NM_002905.3:c.500G>A), causing a missense change (p.Arg167His) in heterozygous state and previously not described pathogenic variant of nucleotic sequence in exon 5 of the RDH5 gene (NM_002905.3:c.838C>T), leading to a missense change (p.Arg280Cys) in heterozygous state with characteristic biomarkers of the disease. Best-corrected visual acuity (BCVA) was 20/20. Nyctalopia was accompanied by reduced b-wave of scotopic (dark-adapted 0.01) ERG and decreased amplitude of a- and b-waves of maximum (dark-adapted 3) ERG. Decreased amplitude of the a- and b-waves of photopic (light-adapted 3) ERG and the amplitude of high-frequency (light-adapted 30 Hz) Flicker ERG shows the involvement of retinal cone system in the process. Fundus autofluorescence imaging of both eyes produced fuzzy and grainy images with slight hyperfluorescence of retinal flecks. Optical coherence tomography showed focal thickening centered in the photoreceptor outer segment corresponding to the multiple discrete albipunctate dots.

[Presentation of a rare case of hereditary hearing loss with X-linked recessive inheritance associated with the POU3F4 gene]. / Opisanie redkogo sluchaya nasledstvennoi tugoukhosti s Kh-stseplennym retsessivnym tipom nasledovaniya, assotsiirovannoi s genom POU3F4.

Congenital hearing loss is one of the most frequent inherited human pathologies, occurring in 1-2 out of 1000 newborns. X-linked hearing loss occurs in 1-5% of all congenital hearing impairments. The proband (a man) and his affected brother have profound prelingual non-syndromic neurosensory hearing loss. Their parents are healthy. The aim of the study was to determine the cause of hearing loss in a given family and to assess the population frequency of the revealed pathogenic genetic variant. NGS analysis identified a pathogenic variant c.907C>T (p.Pro303Ser) in the POU3F4 gene mapped to the Xq21.1 locus. This is the second case of X-linked hearing loss (DFNX2, OMIM 304400) in Europe, caused by the c.907C>T variant in the POU3F4 gene. DFNX2-hearing loss is manifested with abnormalities of the inner ear, predisposing to the "gusher effect" - otoliquorrhea during stapedoplasty. The brother was diagnosed with a c.907C>T variant in the POU3F4 gene in the hemizygous state while in their mother - in the heterozygous state. Their father had no variant c.907C>T. Molecular genetic analysis showed that the genetic variant c.907C>T was not detected in the control sample of healthy female from the Nogai population, which suggests its low frequency in the population.

[Main methodological approaches to the identification and diagnosis of monogenic hereditary diseases and problems in the organization of medical care and unified preventive programs].

In order to optimize economic and organizational technologies for the provision of medical care to the population and to increase the effectiveness of preventive programs, an analysis of the accumulated morbidity and prevalence of monogenic hereditary diseases (MHDs) has been carried out in 13 federal subjects of the Russian Federation representing 11 ethnic groups: Russians of 6 regions, Tatars, Maris, Chuvashs, Bashkirs, Udmurts, Abazins, Adygeans, Nogays, Circassians and Karachays. The study of the population was carried out according to the developed protocol of complex genetic and epidemiological studies in the Research Center for Medical Genetics, which remains unchanged throughout the study. Here we have studied the structure of the genetic load and diversity of MHDs depending on the prevalence of diseases and in accordance with the classification by organ and system types of disease: neurological, ophthalmological, genodermatosis, skeletal, hereditary syndromes, and other hereditary pathology (metabolic hereditary diseases, disorders of blood, hearing, etc.). It is shown that the maximum number of patients (61.81%) falls in the group of frequent forms of MHDs, which differ by federal subjects / ethnic groups of the Russian Federation. There are frequent forms of MHDs for all populations, and "specific" forms for particular federal subjects of the Russian Federation/ethnic groups. Only for a small group of hereditary diseases there is treatment. Most of the detected diseases-psychiatric, neurological, hematological, and hereditary syndromes-significantly reduce life expectancy. Hereditary diseases of the skeleton, eyes, ears and metabolism affect the quality of life, adaptation in society and public health. On average, 65% of patients are diagnosed with MHDs for the first time. This situation implies changes in medical thinking, changes in education and development of both common for all regions and specific prevention programs. Thus, fundamental research in medicine can improve the quality of medical services and contribute to the improvement of public health.

[Molecular and genetic aspects of age-related macular degeneration and glaucoma]. / Molekuliarno-geneticheskie aspekty vozrastnoi makuliarnoi degeneratsii i glaukomy.

In most cases, age-related macular degeneration (AMD) and glaucoma are considered multi-factor diseases that lead to irreversible blindness in senior population of developed countries. Among different types of these diseases, around 5% are monogenic. Studying their molecular and genetic aspects can lay the basis for improvement of diagnostic methods, prognosis of the risks of development, manner of progression and treatment outcomes, as well as creation of new therapy methods. The article reviews modern understanding of the etiopathogenesis of AMD and glaucoma and describes their interrelations.

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus.

BACKGROUND: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed. METHODS: Molecular genetic analysis of 34 CFTR mutations (representing approx. 80-85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common "Russian" mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated. RESULTS: High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency - 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22-7-16-13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA. CONCLUSIONS: The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations.

Congenital aniridia is a severe autosomal dominant congenital panocular disorder, mainly associated with pathogenic variants in the PAX6 gene. The objective of the study was to investigate the mutational and clinical spectra of congenital aniridia in a cohort of 117 patients from Russia. Each patient underwent detailed ophthalmological examination. From 91 unrelated families, 110 patients were diagnosed with congenital aniridia and 7 with WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, and mental Retardation syndrome). The clinical presentation in aniridia patients varied from the complete bilateral absence of the iris (75.5%) to partial aniridia or iris hypoplasia (24.5%). Additional ocular abnormalities were consistent with previous reports. In our cohort, we saw a previously not described high percentage of patients (45%) who showed non-ocular phenotypes. Prevalence of deletions coherent with WAGR syndrome appeared to be 19.4% out of sporadic patients. Among the other aniridia cases, PAX6 deletions were identified in 18 probands, and small intragenic changes were detected in 58 probands with 27 of these mutations being novel and 21 previously reported. In 3 families mosaic mutation was transmitted from a subtly affected parent. Therefore, PAX6 mutations explained 96.7% of aniridia phenotypes in this study with only 3 of 91 probands lacking pathogenic variants in the gene.

[Diagnostic capabilities of optical coherence tomography and confocal laser scanning microscopy in studying manifestations of aniridia-associated keratopathy]. / Diagnosticheskie vozmozhnosti opticheskoi kogerentnoi tomografii i lazernoi skaniruiushchei konfokal'noi mikroskopii v izuchenii proiavlenii aniridiinoi keratopatii.

AIM: to investigate the possible use of anterior segment optical coherence tomography (AS-OCT) and laser scanning confocal microscopy (LSCM) for visualization of limbal progenitor structures and epithelial changes at different stages of aniridia-associated keratopathy (AAK) and to analyze genotype-phenotype correlations of corneal damage. MATERIAL AND METHODS: Thirty-four patients (63 eyes) with congenital aniridia (CA) were subjected to epithelial cell density measurement in the central cornea as well as epithelial surface assessment with limbal palisades of Vogt (POV) detection in the corresponding sites of the two corneas. For that, LSCM (HRT3) and AS-OCT (RTVue XR Avanti) were performed. Central corneal and epithelial thicknesses were measured using the Pachymetry protocol. RESULTS: There has been found an increase in the central corneal thickness (CCT) of CA patients, which correlated with the stage of AAK, and a decrease in the central epithelial thickness as compared with healthy subjects (p<0.05). The difference between the basal and wing epithelial cells density in eyes with stages I and II AAK and normal cells density at stage 0 AAK was statistically significant (p<0.05). Intact or disturbed POV were detected in all patients with PAX6 3' deletion. At that, AS-OCT findings highly agreed with LSCM images for both the inferii (rS=0.85, p<0.05) and superior limbi (rS=0.53, p<0.05). A negative correlation was established between the stage of AAK and in vivo morphology of POV (rS=-0.5, p<0.05). However, no correlation was found between the stage of AAK and patient's age (rS=0.169, p=0.174). CONCLUSION: AS-OCT and LSCM are both important diagnostic tools for corneal surface monitoring in patients with limbal stem cells deficiency.

[Marriage and Migratory Characteristic of Circassians (Late 20th Century)].

This paper analyzes 2052 marriage records for 1990-2000 in the Khabezsky district of Karachay-Cherkessia. The main marriage and migration characteristics of Circassians are studied: index of endogamy, ethnic mar- riage assortativity, intensity of metisation, and Malecot's parameters of isolation by distance.

Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.

[Marriage and Migratory Characteristics of the Urban Population of Karachay-Cherkessia (the End of the 20th Century)].

As part of systematic research carried out by the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics, the marriage and migratory structure of the urban population of Karachay-Cherkessia was studied. Numerical estimates of the population-genetic parameters were obtained from 11346 marriage records for 1990-2000. The endogamy, ethnic assortativeness, miscegenation and local inbreeding intensities, and mean-square migration for the four cities--Cherkessk, Karachayevsk, Ust-Dzheguta, and Teberda were estimated. It is shown that the autochthonic urban population is highly miscegenated, despite the traditional preference for monoethnic marriages. Half of the Russian urban population is migrant; the autochthonic urban population is substantially formed of Karachay-Cherkessia natives of.

High prevalence of W1282x mutation in cystic fibrosis patients from Karachay-Cherkessia.

Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease. The spectrum and frequency of CFTR mutations vary significantly in different populations and ethnic groups. A genetic epidemiological study was conducted in the indigenous ethnic group of people known as the Karachais. They live in the Republic of Karachay-Cherkessia, which lies in the northwest of Russia's North Caucasus region. Karachai's are Turkic-speaking and consist of 194 thousand people (approximately 40% of the population of the Republic). Molecular genetic analysis was performed in 10 unrelated Karachai families with CF patients from three districts in the Republic. A high frequency of W1282X mutation was found (18 of 20 mutant alleles): eight patients were homozygous for the W1282X mutation, and two were compound heterozygous (the second alleles were R1066C and R709X). Analysis for 13 common CF mutations in the sample of 142 healthy Karachais identified two 1677delTA and two W1282X mutation carriers. Thus, the most common CFTR mutation, F508del, was not detected among the CF patients or in healthy Karachais. The most frequent mutation among Karachai patients is W1282X (90%). Its frequency in healthy Karachais is approximately 0.007. Haplotype analysis using the CFTR intragene DNA markers IVS1CA, IVS6aGATT, IVS8CA and IVS17bCA showed that the origins of the W1282X mutation in Karachay-Cherkessia and the Eastern European part of Russia are different.

[Ethnic Marriage Assortativeness and Intensity of Metisation of Karachays].

On the basis of 11,280 marriage records of four regions of Karachay-Cherkessia (Karachaevsky, Malokarachaevsky, Ust-Dzhegutinsky, Prikubansky, 193.2 thousand people in total) for 1990-2000, the intensity of Karachay cross-breeding was determined, amounting to 11.7%. Comparison of the intensity of Karachay cross-breeding with that for some other ethnoses is carried out. The ethnic assortativness H is approximately one. The population is characterized a preference for monoethnic marriages. The endogamy index in the studied regions varies from 0.29 to 0.53; after the exclusion from the analysis of repatriates, it increases to 0.34-0.63. The values of local inbreeding in an interval are 0.0001-0.0004, and no differences in terms of isolation by distance are revealed among the regions (0.01). The average square migration is 40-60 km.