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.

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.

Santrauka. Tyrimo tikslas. Įvertinti bevandenio laikotarpio (BL) trukmės reikšmę naujagimių, gimusių 24–32 gestacijos savaitę, baigtims. Tyrimo metodai. Atliktas retrospektyvusis kohortinis tyrimas. Nagrinėti Vilniaus universiteto ligoninės Santaros klinikose 2014–2016 m. gyvų gimusių 24–32 gestacijos savaitę naujagimių duomenys, kai BL ≥24 val. (N=57). Tiriamieji suskirstyti į grupes pagal bevandenio laikotarpio trukmę: 24–72 val. (N=17) ir ≥72 val. (N=40) bei pagal gestacijos amžių – 24–28 savaičių (N=22) ir 29–32 savaičių (N=35). Rezultatai. Nustatyta ilgesnė bevandenio laikotarpio trukmė naujagimių, kuriems diagnozuota įgimta infekcija (148,1±113,12 val. ir 91,8±48,5 val., p=0,025), mikrobiologiškai patvirtintas sepsis (215,3±32,04 val. ir 123,5±99,1 val., p=0,029), intraskilvelinės kraujosruvos (151,7±117,31 val. ir 119±91,43 val., p=0,000). Nustatytas atvirkštinis moters kraujo C-reaktyviojo baltymo koncentracijos ir bevandenio laikotarpio trukmės tarpusavio ryšys naujagimiams, kuriems diagnozuotos intraskilvelinės kraujosruvos (p=0,0312, r=-0,5565). Mažesnio gestacijos amžiaus naujagimiai dažniau sirgo įgimta infekcija, jiems dažniau taikyta sustiprinta antibakterinė terapija, dirbtinė plaučių ventiliacija, gydymas surfaktantu. 29–32 savaitę GA grupėje nustatytas BL trukmės ir įgimtos infekcijos, sepsio, sustiprinto antibakterinio gydymo, surfaktanto poreikio tarpusavio ryšys. Išvados. Naujagimių, kuriems diagnozuota įgimta infekcija, mikrobiologiškai patvirtintas sepsis, intraskilvelinės kraujosruvos, bevandenis laikotarpis buvo ilgesnis. Jeigu 29–32 neštumo savaitę plyšta vaisiaus dangalų vandenys, turetų buti apsvarstoma galimybė neštumą užbaigti anksčiau.

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.