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Barth syndrome (BTHS) is a rare X-linked disease characterized by dilated cardiomyopathy, proximal skeletal myopathy and cyclic neutropenia. It is caused by various mutations in the tafazzin (TAZ) gene located on Xq28 that results in remodeling of cardiolipin and abnormalities in mitochondria stability and energy production. Here we report on a novel c.285-1G>C splice site mutation in intron 3 of the TAZ gene that was detected prenatally.

Coronary heart disease (CHD) is a complex and heterogeneous cardiovascular disease. There are many genome-wide association studies (GWAS) performed worldwide to extract the causative genetic factors. Moreover, each population may have some exceptional genetic characteristic. Thus, the background of our study is from the previous Lithuanian studies (the LiVicordia Project), which demonstrated the differences of the atherosclerosis process between Lithuanian and Swedish male individuals. In this study we performed GWAS of 32 families of Lithuanian origin in search of significant candidate genetic markers [single nucleotide polymorphisms (SNPs)] of CHD in this population. After careful clinical and biochemical phenotype evaluation, the ~770K SNPs genotyping (Illumina HumanOmniExpress- 12 v1.0 array) and familial GWAS analyses were performed. Twelve SNPs were found to be significantly associated with the CHD phenotype (p value 0.65). The odds ratio (OR) values were calculated. Two SNPs (rs17046570 in the RTN4 gene and rs11743737 in the FBXL17 gene) stood out and may prove to be important genetic factors for CHD risk. Our results correspond with the findings in other studies, and these two SNPs may be the susceptibility loci for CHD

Background: Although copy number variation (CNV) has received much attention, knowledge about the characteristics of CNVs such as occurrence rate and distribution in the genome between populations and within the same population is still insufficient. In this study, Illumina 770 K HumanOmniExpress-12 v1.0 (and v1.1) arrays were used to examine the diversity and distribution of CNVs in 286 unrelated individuals from the two main ethnolinguistic groups of the Lithuanian population (Aukštaièiai and Žemaièiai) (see Additional file 3). For primary data analysis, the Illumina GenomeStudio? Genotyping Module v1.9 and two algorithms, cnvPartition 3.2.0 and QuantiSNP 2.0, were used to identify high-confidence CNVs. Results: A total of 478 autosomal CNVs were detected by both algorithms, and those were clustered in 87 copy number variation regions (CNVRs), spanning ~12.5 Mb of the genome (see Table 1). At least 8.6% of the CNVRs were unique and had not been reported in the Database of Genomic Variants. Most CNVRs (57.5%) were rare, with a frequency of <1%, whereas common CNVRs with at least 5% frequency made up only 1.1% of all CNVRs identified. About 49% of non-singleton CNVRs were shared between Aukštaièiai and Žemaièiai, and the remaining CNVRs were specific to each group. Many of the CNVs detected (66%) overlapped with known UCSC gene regions. Conclusions: The ethnolinguistic groups of the Lithuanian population could not be differentiated based on CNV profiles, which may reflect their geographical proximity and suggest the homogeneity of the Lithuanian population. In addition, putative novel CNVs unique to the Lithuanian population were identified. The results of our study enhance the CNV map of the Lithuanian population. [ABSTRACT FROM AUTHOR]

Timber is predominant resource of the biomass used for the purposes of energy production. Recently, plantations of medium rotation trees of hybrid species have been increasingly cultivated in order to produce timber to be used as a bio-fuel. Coppice plantations are cultivated on the basis of intense techniques in order to achieve accelerated wood production or any other production related to woody crops. Plant growth period of long rotation trees amounts for nearly 30-60 years, whereas that of medium rotation trees of hybrid species - only 15-20 years. Physical characteristics of chaffs of the following medium rotation energy plants have been determined: Quaking aspen (PopulusTremula), Robinia and the wild cherry tree (Pseudoacacia). The main fraction of the timber chipped using Pezzolato drum chipper has been comprised of the 8-16 mm sized particles. The ash content of medium rotation energy plants was found to be low: amounted from 1.87 % (of the wild cherry tree) to 2.4 % (of Robinia), whereas calorific values of the plants under investigation were found to be rather high: amounting for approx. 18.7 MJ/kg. These are close to calorific values of birch which is considered to be the main benchmark or reference in Lithuania. Change in bulk density was found under variable moisture content of wood. Comparison to the bulk density of the absolutely dry wood shows the density of aspen and wild sweet cherry to be rather similar and vary only in range of error; whereas density of robinia is by 3-4 % lower. Increase in moisture content resulted in bulk density of all the sorts of wood to increase in a very similar manner, consequently it was assumed to be identical in all the calculations made. Decrease in moisture content resulted in increase of collapse (fall) angle: of aspen - from 62 to 77°, of robinia - from 90 to 115°, wild sweet cherry - from 65 to 82°. Lower effect of moisture content was found on the valued of flowing angle. It respectively varied as follows: of aspen - from 34 to 40°, of robinia - from 34 to 40°, of wild sweet cherry - from 36 to 42°. [ABSTRACT FROM AUTHOR]

For research investigations were used the herbal unconventional energy plants - cup plant (Silphium perfolatium L.) and Virginia mallow (Sida hermaphrodita), which were grown in Lithuanian Research Centre for Agriculture and Forestry, and the knotweed (Reynoutria), which grew naturally in the forest glade. The productivity of these herbaceous plants are very high - 7-20 t ha-1 dry mass yield. Plants were cut by manual motorized chainsaw and chopped by drum chopper. Prepared chaff was milled by hummer mill and produced mill was granulated by small capacity granulator (250-300 kg ha-1). In presented work were determined investigated plant mill and pellet properties. After investigation of mill fractional composition was determined, that the smallest mill fraction was produced of milled knotweed plant stems: the biggest mill fraction accumulated on sieve with holes 0.25 mm diameter - 45.4 %, and dust - 46.7 %. The cup plants mill biggest fraction accumulated on sieve with holes 0.63 mm (37.6 %), Virginia mallows mill - on sieve with holes 0.5 mm (45.9 %). Also it was determined pellets quality parameters: humidity, density, ash content and calorific value. Determined biggest humidity was of knotweed - 22.3 %, it was too big, but produced knotweed pellets was sufficient hard and burning efficiency was a normal. The pellet density was significant high and ranged from 945.5 to 1072.3 kg m-3 dry matter (DM). The ash content of investigated plant pellets varied from 4.28 to 9.96 %, and was too high compared with wood. The average calorific value of investigated energy plants pellets varied from 16.8 to 17.7 MJ kg-1. Using laboratory equipment INSTRON 5960 were determined pellet disintegration force: the biggest force was for knotweed plant - 847 N, and about two times less for cup plant (463 N) and Virginia mallow (344 N). After analysis of test results it should be concluded, that knotweed pellets are sufficiently resistant to static force. [ABSTRACT FROM AUTHOR]

The efficiency of silage compaction of the chopped mass of maize and grass mixtures by means of centrifugal direct action vibrators was experimentally evaluated in the reported study. The results indicate that the layer of grass plant chaff undergoes intensive compaction for the duration of 5-10 min. The dependences of the density variation of maize and grass plant mixture mass on compaction duration were determined. After 20 min of maize compaction, both silage layers of 510 kg m-3 density (the density of the dry matter - 143 kg m-3) were achieved. Moreover, while mixture of maize and fodder goat's rue (3:1) was compacted, a high mixture density was reached as well. After 10 min of compaction, 474 kg m-3 (166 kg m-3 DM) density was obtained. Analysis of silage quality indicates that maize mixtures (fodder goat's rue (3:1) and maize - red clover (1:1) silage), which were compacted with centrifugal direct-action vibrator, meet the requirements for the high quality silage. [ABSTRACT FROM AUTHOR]

We provide a detailed clinical and molecular analysis of 2 patients with de novo interstitial duplications at 2p14-p16.1 and 2p16.1-p22.1. The 10.13-Mb duplication of chromosome 2p14-p16.1 was identified in a 9-year-old boy with mental retardation, behavioral problems (hyperactivity, hyperphagia, and subsequent vomiting), recurrent respiratory tract infections, macrocephaly, epilepsy, and dysmorphic features. The 17.49-Mb duplication of 2p16.1-p22.1 was found in a 17-year-old girl with moderate mental retardation, behavioral and emotional problems, anxiety, and facial dysmorphic features. Very few cases of de novo interstitial duplication of 2p14-p22.1 are reported in the literature, with the great majority of them lacking a detailed molecular analysis. The abnormal phenotype of these cases is caused by mechanisms such as the overdose of a duplicated gene (or genes), the disruption of a gene or its regulatory sequence by the breakpoints of duplication, or by an excess of genetic material which may disorganize chromatin conformation affecting distant gene expression. The clinical and molecular analysis of these 2 rare de novo interstitial duplications provides useful information which is extremely valuable for clinical evaluation at the prenatal and postnatal level and for the molecular understanding of the underlying mechanisms of human diseases. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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The genetic composition of the Lithuanian population was investigated by analysing mitochondrial DNA hypervariable region 1, RFLP polymorphisms and Y chromosomal biallelic and STR markers in six ethnolinguistic groups of Lithuanians, to address questions about the origin and genetic structure of the present day population. There were no significant genetic differences among ethnolinguistic groups, and an analysis of molecular variance confirmed the homogeneity of the Lithuanian population. MtDNA diversity revealed that Lithuanians are close to both Slavic (Indo-European) and Finno-Ugric speaking populations of Northern and Eastern Europe. Y-chromosome SNP haplogroup analysis showed Lithuanians to be closest to Latvians and Estonians. Significant differences between Lithuanian and Estonian Y chromosome STR haplotypes suggested that these populations have had different demographic histories. We suggest that the observed pattern of Y chromosome diversity in Lithuanians may be explained by a population bottleneck associated with Indo-European contact. Different Y chromosome STR distributions in Lithuanians and Estonians might be explained by different origins or, alternatively, be the result of some period of isolation and genetic drift after the population split. [ABSTRACT FROM AUTHOR]

Intellectual disability is a broad diagnosis encompassing a wide variety of overlapping phenotypes and severities. Genetic etiologies are found in approximately two-thirds of cases with underlying mutations ranging from large cytogenetic aberrations to point mutations and even epigenetic alterations. Diagnostic is challenging, be cause these conditions are genetically heterogenous with many different genetic alterations, which may manifest in clinically indistinguishable phenotypes. The diagnostic success often depends on diagnostic workflow of the patient. During the last few years enormous technical progress has been achieved in the area of molecular cytogenetics and molecular genetics, changing the recommendations of evaluation of children with intellectual disability. The stepwise approach of diagnostic evaluation increases the diagnostic yield and makes the use of expensive tools more rational. An optimal diagnostic evaluation starts with family history and genealogy, personal history and clinical evaluation, followed by differential diagnosis. When a specific genetic disorder is suspected, the confirmatory tests must be performed. However, according to the literature, in 65-85% of patients with ID no specific genetic/metabolic disorder is suspected after the first step of evaluation or the suspected diagnosis cannot be confirmed. In that case it is always important to look for additional clinical findings, and firstly the neuroimaging is recommended. If still no specific genetic disorder is suspected, molecular karyotyping is recommended, followed by X-linked genetic testing. Finally, screening for in born errors of metabolism in children with ID is indicated. However, even if all currently available diagnostic methods were applied, there would remain patients with intellectual disability of undetermined cause, and not always the appropriate tests for the suspected genetic disorders are available. In all these cases, where possible, it is important to store patient's cell line or DNA. Systematic follow-up of the patient should be carried out routinely. Further technical advances are necessary to enable investigation of other genetic mechanisms, including somatic mutation, epigenetic dysregulation and polygenic disruption, each of which is likely to account for a significant proportion of cases. [ABSTRACT FROM AUTHOR]

Leigh syndrome or subacute necrotizing encephalomyelopathy is one of the most common mitochondrial diseases in childhood. It is a progressive neurodegenerative disease with focal symmetric brain lesions mainly in the basal ganglia, thalamus, and brainstem which appear as hyperintense lesions on T2-weighted MRI. Presenting symptoms are mainly those of central or peripheral ner vous system, sometimes patients have dysmorphic features, cardiomyopathy signs, gastrointestinal, and kidney signs. The spectrum of neurological symptoms is wide from severe in fantile disease to subtle clinical manifestations. Psychomotor deay, seizures, ataxia, opticathrophy, dystonia, respiratory in sufficiency, polyneuropathy, and myopathy are the most frequent. Mutations in the genes encoding mitochondrial proteins are responsible for this syndrome, molecular genetic analyses confirm the diagnosisinal most 50% of Leigh syndrome patients. Clinical presentation, diagnostics and treatment issues are discussed in the article, also a case of Leigh syndrome is presented. The disease revealed itself during the first months of age with psychomotor delay, in fantile spasms, myopathy, swallow ing problems and respiratory failure. Hyperintense lesions on T2-weighted head MRI were found. Activity of pyruvate dehydrogenase complex activity was found to be de creased in myocytes and skin fibroblasts. Diagnosis of pyruvate dehydrogenase deficiency was further confirmed by moleculargenetic analysis of PDHA1 gene: a missense mutation (p.Arg378His) was found in the 11th exon of this gene. The disease course and applied treatment with ketogenic dieta as well as efficacy of this treatment is presented. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship among Lithuanian, Latvian, Indian, and some other populations through a genome-wide data analysis of single nucleotide polymorphisms (SNPs). Limited data of Baltic populations were mostly compared with geographically closer modern and ancient populations in the past, but no previous investigation has explored their genetic relationships with distant populations, like the ones of India, in detail. To address this, we collected and merged genome-wide SNP data from diverse publicly available sources to create a comprehensive dataset with a substantial sample size especially from Lithuanians and Latvians. Principal component analysis (PCA) and admixture analysis methods were employed to assess the genetic structure and relationship among the populations under investigation. Additionally, we estimated an effective population size ( Ne ) and divergence time to shed light on potential past events between the Baltic and Indian populations. To gain a broader perspective, we also incorporated ancient and modern populations from different continents into our analyses. Our findings revealed that the Balts, unsurprisingly, have a closer genetic affinity with individuals from Indian population who speak Indo-European languages, compared to other Indian linguistic groups (such as speakers of Dravidian, Austroasiatic, and Sino-Tibetan languages). However, when compared to other populations from the European continent, which also speak Indo-European and some Uralic languages, the Balts did not exhibit a stronger resemblance to Indo-European-speaking Indians. In conclusion, this study provides an overview of the genetic relationship and structure of the populations investigated, along with insights into their divergence times., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Daniūtė, Pranckėnienė, Pakerys, Kloviņš, Kučinskas and Urnikytė.)

Genomic effect variants associated with survival and protection against complex diseases vary between populations due to microevolutionary processes. The aim of this study was to analyse diversity and distribution of effect variants in a context of potential positive selection. In total, 475 individuals of Lithuanian origin were genotyped using high-throughput scanning and/or sequencing technologies. Allele frequency analysis for the pre-selected effect variants was performed using the catalogue of single nucleotide polymorphisms. Comparison of the pre-selected effect variants with variants in primate species was carried out to ascertain which allele was derived and potentially of protective nature. Recent positive selection analysis was performed to verify this protective effect. Four variants having significantly different frequencies compared to European populations were identified while two other variants reached borderline significance. Effect variant in SLC30A8 gene may potentially protect against type 2 diabetes. The existing paradox of high rates of type 2 diabetes in the Lithuanian population and the relatively high frequencies of potentially protective genome variants against it indicate a lack of knowledge about the interactions between environmental factors, regulatory regions, and other genome variation. Identification of effect variants is a step towards better understanding of the microevolutionary processes, etiopathogenetic mechanisms, and personalised medicine.

The adverse effects on the health of the Chornobyl nuclear power plant accident clean-up workers have been reported previously. However, there is a lack of studies on the mental health of Chornobyl clean-up workers. The current study explored psychological distress in a sample of Lithuanian clean-up workers 35 years after the accident. In total, 107 Lithuanian Chornobyl clean-up workers (M age  = 62.5) and 107 controls were included in the study. The Hospital Anxiety and Depression Scale (HAD) was used for the assessment of anxiety and depression. The depression symptoms were significantly higher in the clean-up workers compared to the control group. The prevalence of severe depression symptoms was 23.4% and 4.7% in the Chornobyl clean-up workers and control groups, respectively. The risk for severe depression was associated with Chornobyl clean-up work (adjusted OR = 5.9). No differences in the anxiety symptoms were found between clean-up workers and controls. The study revealed the deteriorated mental health of the Lithuanian Chornobyl clean-up workers 35 years after the disaster - in particular, high levels of depression. Psychosocial support programmes for clean-up workers should be provided to mitigate the adverse effects of the disaster.

Pathogens and infectious diseases have imposed exceptionally strong selective pressure on ancient and modern human genomes and contributed to the current variation in many genes. There is evidence that modern humans acquired immune variants through interbreeding with ancient hominins, but the impact of such variants on human traits is not fully understood. The main objectives of this research were to infer the genetic signatures of positive selection that may be involved in adaptation to infectious diseases and to investigate the function of Neanderthal alleles identified within a set of 50 Lithuanian genomes. Introgressed regions were identified using the machine learning tool ArchIE. Recent positive selection signatures were analysed using iHS. We detected high-scoring signals of positive selection at innate immunity genes (EMB, PARP8, HLAC, and CDSN) and evaluated their interactions with the structural proteins of pathogens. Interactions with human immunodeficiency virus (HIV) 1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified. Overall, genomic regions introgressed from Neanderthals were shown to be enriched in genes related to immunity, keratinocyte differentiation, and sensory perception., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Differences in the relative fitness of genomic variants are foundational, without these, neither natural selection nor adaption can exist. This research analyzed two microevolutionary forces, mutations, and positive selection, using whole genome sequencing data from Lithuanians across three generations: newborns (generation I), their parents (generation II), 60 years old Lithuanians, and the root ancestors (generation III). The main objective was to determine the frequency of mutations under selection in modern humans and how allele frequencies change across generations. Our results show that going through all the landscapes of the relative fitness on each chromosome, the general relative fitness background pattern remains the same in analysed generations. However, the tendency of relative fitness to decrease, in general, is noted. We hypothesize that the de novo genome variants or genome variants with a very low frequency that formed in the previous generation did not have time to be as affected by natural selection, thus, in the following generation, the force of natural selection acting on them is greater and their cumulative relative fitness also decreases. The strong natural selection pressure on the genetic regions that encode the NEGR1 and PTPN1/PTNP21 genes were also identified, highlighting the evolution of the Lithuanian population's genome over generations, and possible genomic "deficiencies" for better adaptation., (© 2023. The Author(s).)

Background and Objectives: Heterozygous pathogenic variants in the MED13L gene cause impaired intellectual development and distinctive facial features with or without cardiac defects (MIM #616789). This complex neurodevelopmental disorder is characterised by various phenotypic features, including plagiocephaly, strabismus, clubfoot, poor speech, and developmental delay. The aim of this study was to evaluate the clinical significance and consequences of a novel heterozygous intragenic MED13L deletion in a proband with clinical features of a MED13L -related disorder through extensive clinical, molecular, and functional characterisation. Materials and Methods: Combined comparative genomic hybridisation and single-nucleotide polymorphism array (SNP-CGH) was used to identify the changes in the proband's gDNA sequence (DECIPHER #430183). Intragenic MED13L deletion was specified via quantitative polymerase chain reaction (qPCR) and Sanger sequencing of the proband's cDNA sample. Western blot and bioinformatics analyses were used to investigate the consequences of this copy number variant (CNV) at the protein level. CRISPR-Cas9 technology was used for a MED13L -gene-silencing experiment in a culture of the control individual's skin fibroblasts. After the MED13L -gene-editing experiment, subsequent functional fibroblast culture analyses were performed. Results: The analysis of the proband's cDNA sample allowed for specifying the regions of the breakpoints and identifying the heterozygous deletion that spanned exons 3 to 10 of MED13L , which has not been reported previously. In silico, the deletion was predicted to result in a truncated protein NP&#95;056150.1:p.(Val104Glyfs*5), partly altering the Med13&#95;N domain and losing the MedPIWI and Med13&#95;C domains. After MED13L gene editing was performed, reduced cell viability; an accelerated aging process; and inhibition of the RB1 , E2F1 , and CCNC gene expression were found to exist. Conclusions: Based on these findings, heterozygous intragenic 12q24.21 deletion in the affected individual resulted in MED13L haploinsufficiency due to the premature termination of protein translation, therefore leading to MED13L haploinsufficiency syndrome.

Some people resist or recover from health challenges better than others. We studied Lithuanian clean-up workers of the Chornobyl nuclear disaster (LCWC) who worked in the harshest conditions and, despite high ionising radiation doses as well as other factors, continue ageing relatively healthily. Thus, we hypothesised that there might be individual features encoded by the genome which act protectively for better adaptiveness and health that depend on unique positive selection signatures. Whole-genome sequencing was performed for 40 LCWC and a control group composed of 25 men from the general Lithuanian population (LTU). Selective sweep analysis was performed to identify genomic regions which may be under recent positive selection and determine better adaptiveness. Twenty-two autosomal loci with the highest positive selection signature values were identified. Most important, unique loci under positive selection have been identified in the genomes of the LCWC, which may influence the survival and adaptive qualities to extreme conditions, and the disaster itself. Characterising these loci provide a better understanding of the interaction between ongoing microevolutionary processes, multifactorial traits, and diseases. Studying unique groups of disease-resistant individuals could help create new insights for better, more individualised, disease diagnostics and prevention strategies.

Aim: The aim is to provide an overview of recent research on genetic factors that influence preterm birth in the context of neonatal phenotypic assessment., Methods: This is a nonsystematic review of the recent scientific literature., Results: Maternal and fetal genetic diversity and rare genome variants are linked with crucial immune response sites. In addition, more frequent in preterm neonates, de novo variants may lead to attention deficits, hyperactivity, autism spectrum disorders, and infertility of both sexes later in life. Environmental factors may also greatly burden fetal, and consequently, neonatal development and neurodevelopment through a failure in the fetal epigenome reprogramming process and even influence the initiation of spontaneous preterm pregnancy termination. Minimally invasive analysis of the transcription factors associated with preterm birth helps elucidate labor mechanisms and predict its timing. We also provide valuable summaries of genomic and transcriptomic factors that contribute to preterm birth., Conclusions: Investigation of the human genome, epigenome, and transcriptome helps to identify molecular mechanisms linked with preterm delivery and premature newborn clinical appearance in early and late neonatal life and even predict developmental outcomes. Further studies are needed to fully understand the implications of genetic changes in preterm births. These data could be used to develop targeted interventions aimed at selecting the most effective individual treatment and rehabilitation plan., (© 2022 Japan Society of Obstetrics and Gynecology.)

Schizophrenia has a heritability of 60-80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Most genetic variants are rare and specific to the population, highlighting the importance of characterizing local population genetic diversity. Many countries have initiated population-based whole-genome sequencing (WGS) studies. Genomic variation within Lithuanian families are not available in the public databases. Here, we describe initial findings of a high-coverage (an average of 36.27×) whole genome sequencing for 25 trios of the Lithuanian population. Each genome on average carried approximately 4,701,473 (±28,255) variants, where 80.6% (3,787,626) were single nucleotide polymorphisms (SNPs), and the rest 19.4% were indels. An average of 12.45% was novel according to dbSNP (build 150). The WGS structural variation (SV) analysis identified on average 9133 (±85.10) SVs, of which 95.85% were novel. De novo single nucleotide variation (SNV) analysis identified 4417 variants, where 1.1% de novo SNVs were exonic, 43.9% intronic, 51.9% intergenic, and the rest 3.13% in UTR or downstream sequence. Three potential pathogenic de novo variants in the ZSWIM8 , CDC42EP1 , and RELA genes were identified. Our findings provide useful information on local human population genomic variation, especially for de novo variants, and will be a valuable resource for further genetic studies, and medical implications.

The effect of a variant on an organism is always multifaceted and can be considered from multiple perspectives-biochemical, medical, or evolutionary. However, the relationship between the effects of amino acid substitution on protein activity, human health, and an individual's evolutionary fitness is not trivial. We uncover that the general Lithuanian population is characterized by a "mirror reflection" of the de novo variant fitness effect, confirming the theory of neutrality. Meanwhile, in the group of individuals with intellectual disability, compared with the reference exome de novo variants significantly changed the composition of the amino acid. Therefore, it predicts that, both in terms of the number of amino acids and changes in their relative fitness, the structure of the proteins encoded by the studied amino acids undergo significant changes following the de novo variant, leading to possible changes in protein function associated with phenotypic traits. These results suggest that the analysis of relative fitness of exome sequences with de novo variants can predict the future phenotype. Therefore even in those cases, then only a few of all functional prediction analysis tools predict a variant as damaging, the negative relative fitness or even adaptability of the genome variant should be carefully evaluated considering both its direct function and the global background of the possible disease-associated mechanism regardless of the phenotype being studied., (© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)