Oksana Naumova

University of Houston | U of H, UH · Department of Psychology

Background: In Down syndrome (DS) there is a high occurrence of congenital hypothyroidism (CH) and subclinical hypothyroidism (SH) early in life. The etiology of CH and early SH in DS remains unclear. Previous research has shown genome-wide transcriptional and epigenetic alterations in DS. Thus, we hypothesized that CH and early SH could be caused...

This study provides new data on the whole-exome sequencing of a cohort of children with autistic spectrum disorders (ASD) from an underexplored Russian population. Using both a cross-sectional approach involving a control cohort of the same ancestry and an annotation-based approach involving relevant public databases, we explored exonic single nucl...

Представлены результаты анализа экзомных вариаций в сельской популяции Европейского Севера России. Популяция, исходно возникнув как монастырское поселение, развивалась на протяжении своей полутысячелетней истории в относительной культурной и географической изоляции. Определенную уникальность популяции составляет установленная высокая превалентность...

Among the well-known physiological consequences of early adverse environments is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. A number of studies demonstrate that negative parenting and living with parents with a history of substance abuse and mental health problems may be associated with HPA axis dysregulation in children. In co...

На примере исследования отдельного семейного случая, показано успешное применение экзомного секвенирования семейных трио (ребенок-пробанд и родители) в качестве первого метода геномной диагностики множественных необъясненных нарушений и задержек развития, с целью скриннинга на наличие патогенных однуклеотидных замен и структурных геномных вариантов...

This short report on a family case study provides evidence of the effectiveness of exome sequencing of family trios (proband-parents) as the first-tier test in genomic diagnostics of unexplained developmental delays and disorders, as a genomic screening for both pathogenic single-nucleotide variants and copy number variations (CNVs). In this study,...

Despite substantial grounds for such research, the role of chronic exposure to stressors in the onset and aggravation of learning disabilities (LDs) is largely unexplored. In this review, we first consider the hormonal, (epi)genetic, and neurobiological mechanisms that might underlie the impact of adverse childhood experiences, a form of chronic st...

Recent research has provided evidence on genome-wide alterations in DNA methylation patterns due to trisomy 21, which have been detected in various tissues of individuals with Down syndrome (DS) across different developmental stages. Here, we report new data on the systematic genome-wide DNA methylation perturbations in blood cells of individuals w...

This study, utilizing whole‐exome sequencing (WES), reports on a previously detected disease‐related variant in the androgen receptor gene AR [c.528C>A (p.Ser176Arg)] and novel candidate variants in the DHCR24, BMPR1B, NODAL, and WDR48 genes detected in the genome of a 15‐month‐old child diagnosed with MPH, manifested as partial androgen insensitiv...

Approximately 30% of individuals with autism spectrum disorder (ASD) experience developmental regression, the etiology of which remains largely unknown. We performed a complete literature search and identified 47 genes that had been implicated in such cases. We sequenced these genes in a preselected cohort of 134 individuals with regressive autism....

The etiological mechanisms of the genetic underpinnings of developmental language disorder (DLD) are unknown, in part due to the behavioral heterogeneity of the disorder's manifestations. In this study, we explored an association between the SETBP1 gene (18q21.1), revealed in a genome‐wide association study of DLD in a geographically isolated popul...

Children left without parental care and placed in institutional settings represent a particularly vulnerable group. In the absence of sufficient social interaction, children with experience of early deprivation demonstrate neural, social, and emotional deficits. In the present study, we use electroencephalographic (EEG) techniques to examine the fu...

Recent studies of the genetic foundations of cognitive ability rely on large samples (in extreme, hundreds of thousands) of individuals from relatively outbred populations of mostly European ancestry. Hypothesizing that the genetic foundation of cognitive ability depends on the broader population-specific genetic context, we performed a genome-wide...

Вопрос формирования физиологического и поведенческого фенотипа под воздействием неблагоприятного раннего опыта рассматривается с точки зрения взаимодействия генетического и эпигенетического факторов. На примере двух генов, участвующих в обеспечении нейрогуморального ответа на стресс, а именно гена транспортера серотонина SLC6A4 и гена глюкокортикои...

Цель исследования: изучение влияния опыта курения матерей на показатели физического развития (ФР) детей, оставшихся без попечения родителей или проживающих в семье биологических родителей, при рождении – оценку по шкале Апгар и антропометрические характеристики (вес, рост, окружность головы и груди). Материалы и методы исследования: объем выборки р...

This article reports on new data on the association of breastfeeding with DNA methylation in the peripheral blood cells of 37 children aged from 9 months to four years. Whole-genome DNA methylation profiling was performed using the Illumina Methylation EPIC array. The Epigenome-Wide Association Study (EWAS) revealed an association between the durat...

Представлены данные об ассоциации грудного вскармливания с метилированием ДНК в клетках периферической крови 37 детей в возрасте от 9 мес. до четырех лет. Полногеномные профили метилирования ДНК изучались с помощью биочипа высокой плотности Illumina MethylationEPIC. Поиск полно-эпигеномных ассоциаций позволил выявить связь между продолжительностью...

In this article we present a summary of the literature on the associations between learning difficulties/disabilities and juvenile delinquency. This literature is almost a hundred years old, but, although reportedly demonstrating the low academic achievement–delinquency connection, contains numerous unanswered questions regarding the frequency, str...

Early social deprivation (i.e., an insufficiency or lack of parental care) has been identified as a significant adverse early experience that may affect multiple facets of child development and cause long-term outcomes in physical and mental health, cognition and behavior. Current research provides growing evidence that epigenetic reprogramming may...

Supplemental Figures and Tables

Distributions of standard scores and Z-scores on four adaptive domains from the VABS assessment (Communication, Daily Living Skills, Socialization and Motor Skills) in the combined sample of n = 58 children (top and lateral panels), and the scatterplots for the associations between the standard and Z-scores. (TIF)

Relationships between the two types of methylation values (beta-values and z-values). Top left corner represents the distribution of the pairwise Pearson's r coefficients for k = 164 epigenome-wide significant probes. As an example, we also present scatterplots for three individual CpGs that showed the maximum r close to 1 (the SMO gene), and for t...

Core demographics for the study sample: Children raised in institutional care (IC) and children raised by their biological families (BFC). Child age (in months), duration of institutionalization (in months) at the time of blood draw (AgeEPI) and at the time of assessment (AgeVABS) are presented. (XLSX)

Blood cell type distributions in IC and BFC children (individual data). (XLSX)

List of 172 genes with known functions, which were significantly differentially methylated in the IC group; 87 genes that had a significant (STRING confidence score > .400) interaction with at least one other gene from the list are shown in bold. (XLSX)

Illumina MethylationEPIC probes localized to the CpG island associated with promoter of the glucocorticoid receptor gene, NR3C1, which showed a significant difference (nominal p-value < .05) in methylation levels between the IC and the BFC group. (XLSX)

Heatmap illustrating the clustering of IC and BFC children based on blood cell-type composition estimates derived from DNA methylation data. (TIF)

CpG sites differentially methylated in IC group of children, compared to the BFC group. Individual methylation levels are represented in original beta-values and in betas adjusted on demographic variables, z-values. CpG sites annotation corresponds to Illumina's manifest for the MethylationEPIC microarray. Inter-group differences in CpG methylation...

List of 78 DMESs, whose methylation levels (z-values) had a significant (nominal P-value < .05) correlation with Z-scores for at least one of the four examined adaptive behavior domains according to VABS. Spearman rank correlation coefficients are presented. Coefficients with p < .05 are shown in red; coefficients with p < .01 are shown in bold; th...

Individual scores for the four VABS adaptive behavior domains for institutionalized children (IC; N = 29) and children raised in biological families (BFC; N = 25). SS–standard score. (XLSX)

Impoverished early care environments are associated with developmental defcits in children raised in institutional settings. Despite the accumulation of evidence regarding defcits in general cognitive functioning in this population, less is known about the impact of institutionalization on language development at the level of brain and behavior. We...

This study aimed to examine whether the relationship between mothers’ DNA methylation profiles and offspring’s depression is modulated by negative parenting. The participants were 35 African‐American mother–offspring dyads. Young adult offspring (19 females; age = 17–29.5 years) were assessed on depressive symptoms, and mothers (36–51 years) were a...

Early environmental conditions are known to influence epigenetic patterns in the HPA axis. The present study examined associations between institutional rearing, DNA methylation in the HPA axis and child behavioral outcomes. We tested the association between institutionalization duration and methylation at CpG sites in HPA axis related genes, CRH (...

Проанализированы результаты современных исследований роли метилирования ДНК в эмбриональном развитии человека и влияния табачного дыма при курении матери на эпигенетический статус развивающегося ребенка. Молекулярные механизмы, обеспечивающие связь между материнским курением и его эффектами на развитие и здоровье потомка, особенно отдаленными эффек...

The paper analyzes the results of current studies of the role of DNA methylation during human embryonic development and the effects of maternal smoking on the epigenetic status of a developing child. The molecular mechanisms mediating the association between maternal smoking and its effects on the development and health of the offspring, especially...

The study aims to investigate the long-term epigenetic effects of prenatal tobacco smoke exposure in early childhood. The preliminary results based on a small cohort study are presented.

Epigenetic regulation plays an important role in development, at the embryonic stages and later during the lifespan. Some epigenetic marks are highly conserved throughout the lifespan whereas others are closely associated with specific age periods and/or particular environmental factors. Little is known about the dynamics of epigenetic regulation d...

Key Clinical Message This manuscript reports on genomewide epigenetic alterations in cri‐du‐chat syndrome related to a partial aneusomy of chromosome 5. A systematic analysis of these alterations will open up new possibilities for the prognostic evaluation of CDCS patients and the development of new therapeutic interventions for reducing the severi...

Table S1. List of 191 CpGs, which had a significant (Fold Change > 1.2; FDR adjusted P‐value < 0.05) difference in the methylation level (β‐value) in the participant with Cri‐du‐chat syndrome (CDCS) in comparison to control individuals (CTRL)

Table S2. List of 54 genes that contain an Illumina Human Methyalation450 probe localized within a regulatory element (gene promoter, 5′UTR, and the region 1500 nt upstream of the transcription start site, TSS), which had a significant difference in the methylation level (>1.2 fold change at an FDR adjusted P‐value < 0.05) in the genome of the part...

Table S3. List of genes differentially methylated in Cri‐du‐chat syndrome, which are known to be associated with a human inherited disease or human phenotypic abnormality. Data on the associations are represented based on the OMIM (Online Mendelian Inheritance in Man; https://omim.org/) and the HPO (The Human Phenotype Ontology; http://human-phenot...

Recent research in the field of genomics and epigenetics has provided evidence that alterations in the system of epigenetic regulation are highly involved in the molecular etiology of neurodegenerative and neuropathic disorders. However, there is a gap in knowledge on the epigenetic perturbations that may accompany the CNS impairments during the de...

Исследования в области геномики и эпигенетики установили значимую роль нарушений в системе эпигенетической регуляции в этиологии нейродегенеративных и нейропатических заболеваний. При этом эпигенетические альтерации, сопутствующие нарушениям ЦНС во время внутриутробного развития, таким, как перинатальные энцефалопатии, и их проявления в раннем пост...

The last decade has been marked by an increased interest in relating epigenetic mechanisms to complex human behaviors, although this interest has not been balanced, accentuating various types of affective and primarily ignoring cognitive functioning. Recent animal model data support the view that epigenetic processes play a role in learning and mem...

To date, researcheshave show that a variety of diseases and developmental delays, overrepresented in institutionalized children, are associated with deprivation conditions of baby homes. The epigenome appears to be a molecular mediator that regulates the interaction between the environment and the phenotype. Our preliminary comparative study examin...

This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17–29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income urba...

Этиология Синдрома Дауна (СД) – анеуплоидия по 21 хромосоме, установлена еще в середине XX в., однако, эти структурные нарушения генома в целом не объясняют широкий спектр эндофенотипов СД. Новые перспективы в понимании патофизиологии СД открываются с исследованиями в области эпигеномики. Так, недавние исследования эпигенома эмбриональных тканей и...

The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we sho...

Epigenetic mechanisms, including DNA methylation, that underlie neuropsychiatric conditions have become a promising area of research. Most commonly used DNA sources in such studies are peripheral (whole) blood (WB), saliva (SL), and lymphoblastoid cell lines (LCLs); thus, the question of the consistency of DNA methylation patterns in those cells is...

Gene expression is one of the main molecular processes regulating the differentiation, development, and functioning of cells and tissues. In this review a handful of relevant terms and concepts are introduced and the most common techniques used in studies of gene expression/expression profiling (also referred to as studies of the transcriptome or t...

In recent years, translational research involving humans and animals has uncovered biological and physiological pathways that explain associations between early adverse circumstances and long-term mental and physical health outcomes. In this article, we summarize the human and animal literature demonstrating that epigenetic alterations in key biolo...

The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the...

Previous studies with nonhuman species have shown that animals exposed to early adversity show differential DNA methylation relative to comparison animals. The current study examined differential methylation among 14 children raised since birth in institutional care and 14 comparison children raised by their biological parents. Blood samples were t...

The data on mitochondrial DNA diversity in seven local populations (villages) and four territorial groups of Tatars of the Tobol-Irtysh basin are presented. In the Turkic-speaking populations from the Tobol and Irtysh river basins, high levels of intergroup and interpopulation mtDNA variation were observed. It was demonstrated that genetic diversit...

New data on mitochondrial DNA polymorphism in the representatives of Kazym territorial group of Northern Khanty are presented. MtDNA diversity observed in Kazym Khanty was compared with that in Khanty from Shuryshkarskii raion of Yamalo-Nenets Autonomous Okrug.

Genetic differentiation of the population of Russia is investigated. The work is based on data about immuno-biochemical and molecular markers polymorphism in about 1,500 populations from 62 ethnoses belonging to six main linguistic families and having different cultural traditions. Genetic diversity is studied by cartographic and statistical method...

Previous studies of Y chromosome variation have revealed that western Europe, the Volga-Ural region, and the Caucasus differ dramatically with respect to Y-SNP haplogroup composition. The European part of Russia is situated in between these three regions; to determine if these differences reflect clines or boundaries in the Y-chromosome landscape,...

A total of 17 Y-specific STR loci were studied in 12 districts of the European part of Russia aiming to ascertain the amount of substructure required for the construction of a representative regional database. All groups exhibited high haplotype diversities but low inter-population variance as measured by an analysis of molecular variance. However,...

Data on the variation of the nucleotide sequence of hypervariable segment I (HVSI) and restriction fragment length polymorphism (RFLP) of the coding region of mitochondrial DNA (mtDNA) have been used to characterize the mitochondrial gene pool of Siberian Tatars of the Tobol-Irtysh basin (N = 218), one of three geographic/linguistic groups of Siber...

New data on mitochondrial DNA polymorphism among Russian population from five oblasts, located within the main ethnic area of Russians, specifically, Ryazan' oblast, Ivanovo oblast, Vologda oblast, Orel oblast, and Tambov oblast (N = 177) are presented. RFLP analysis of the mtDNA coding region showed that most of the mtDNA diversity in the populati...

New data on mitochondrial DNA polymorphism among Russian population from five oblasts, located within the main ethnic area of Russians, specifically, Ryazan' oblast, Ivanovo oblast, Vologda oblast, Orel oblast, and Tambov oblast (N = 177) are presented. RFLP analysis of the mtDNA coding region showed that most of the mtDNA diversity in the populati...

Ossetians are a unique group in the Caucasus, in that they are the only ethnic group found on both the north and south slopes of the Caucasus, and moreover they speak an Indo-European language in contrast to their Caucasian-speaking neighbours. We analyzed mtDNA HV1 sequences, Y chromosome binary genetic markers, and Y chromosome short tandem repea...

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. Mo...

On the basis of analysis of mtDNA from skeletal remains, dated by 14C 4020-3210 BC, from the Ust'-Ida I Neolithic burial ground in Cis-Baikal area of Siberia, we obtained genetic characteristics of the ancient Mongoloid population. Using the 7 restriction enzymes for the analysis of site's polymorphism in 16,106-16,545 region of mtDNA, we studied t...

Nineteen mtDNA samples from osseous remains found in the Ust-Ida I burial ground (middle Angara River) were analyzed. An ancient population dated back to 4020-3210 B.C. by radiocarbon (14C) analysis and archeologically assigned to the Neolithic Isakovo culture of the Baikal region was described in terms of molecular genetics. Data on restriction-si...

A computer software package has been created that assists studying restriction fragment length polymorphism (RFLP). The software simulates and analyzes the results of amplification by means of polymerase chain reaction (PCR) followed by restriction of amplification products, as well as the results of nucleic acid electrophoresis.