Sequencing and annotated analysis of an Estonian human genome

Lilleoja, Rutt; Sarapik, Aili; Reimann, Ene; Reemann, Paula; Jaakma, Ülle; Vasar, Eero; Kõks, Sulev

doi:10.1016/j.gene.2011.11.022

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…Likewise, the VNTRs are recognized as common polymorphisms that are responsible for the large part of the genomic variation. 23 In our previous study, we identified the interaction between two VNTRs at the SLC6A4 locus in regulating nicotine dependence. 16 This interaction reflects the functional reciprocal regulation of transcriptional activity between these VNTRs.…”

Section: Discussionmentioning

confidence: 99%

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Kõks¹,

Prans

et al. 2020

Exp Biol Med (Maywood)

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Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence. Impact statement The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example. Another impact is that we analyzed the genetic variability in the Asian population and therefore our data present a piece of information from underrepresented populations.

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Section: Discussionmentioning

confidence: 99%

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Kõks¹,

Prans

et al. 2020

Exp Biol Med (Maywood)

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“…The increased accessibility of DNA sequencing has contributed to individual efforts from a range of distinct populations. To date, individual genomes from American [11, 12], Han Chinese [13], Russian [14], Khoisan [15], Bantu [15], Japanese [16], German [17], Gujarati Indian [18], Estonian [19], Pakistani [20] and Mongolian [21] populations have been sequenced and analyzed, among many others [1].…”

Section: Introductionmentioning

confidence: 99%

The sequencing and interpretation of the genome obtained from a Serbian individual

et al. 2018

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Recent genetic studies and whole-genome sequencing projects have greatly improved our understanding of human variation and clinically actionable genetic information. Smaller ethnic populations, however, remain underrepresented in both individual and large-scale sequencing efforts and hence present an opportunity to discover new variants of biomedical and demographic significance. This report describes the sequencing and analysis of a genome obtained from an individual of Serbian origin, introducing tens of thousands of previously unknown variants to the currently available pool. Ancestry analysis places this individual in close proximity to Central and Eastern European populations; i.e., closest to Croatian, Bulgarian and Hungarian individuals and, in terms of other Europeans, furthest from Ashkenazi Jewish, Spanish, Sicilian and Baltic individuals. Our analysis confirmed gene flow between Neanderthal and ancestral pan-European populations, with similar contributions to the Serbian genome as those observed in other European groups. Finally, to assess the burden of potentially disease-causing/clinically relevant variation in the sequenced genome, we utilized manually curated genotype-phenotype association databases and variant-effect predictors. We identified several variants that have previously been associated with severe early-onset disease that is not evident in the proband, as well as putatively impactful variants that could yet prove to be clinically relevant to the proband over the next decades. The presence of numerous private and low-frequency variants, along with the observed and predicted disease-causing mutations in this genome, exemplify some of the global challenges of genome interpretation, especially in the context of under-studied ethnic groups.

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Sequencing and annotated analysis of the Holstein cow genome

et al. 2013

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The aim of our study was to create a high-quality Holstein cow genome reference sequence and describe the different types of variations in this genome compared to the reference Hereford breed. We generated one fragment and three mate-paired libraries from genomic DNA. Raw files were mapped and paired to the reference cow (Bos taurus) genome assemblies bosTau6/UMD_3.1. BioScope (v1.3) software was used for mapping and variant analysis. Initial sequencing resulted in 2,842,744,008 of 50-bp reads. Average mapping efficiency was 78.4 % and altogether 2,168,425,497 reads and 98,022,357,422 bp were successfully mapped, resulting in 36.7X coverage. Tertiary analysis found 5,923,230 SNPs in the bovine genome, of which 3,833,249 were heterozygous and 2,089,981 were homozygous variants. Annotation revealed that 4,241,000 of all discovered SNPs were annotated in the dbSNP database and 1,682,230 SNPs were considered as novel. Large indel variations accounted for 48,537,190 bp of the entire genome and there were 138,504 of them. The largest deletion was 18,594 bp and the largest insertion was 13,498 bp. Another group of variants, small indels (n = 458,061), accounted for the total variation of 1,839,872 nucleotides in the genome. Only 92,115 small indels were listed in the dbSNP and therefore 365,946 small indels were novel. Finally, we identified 1,876 inversions in the bovine genome. In conclusion, this is another description of the Holstein cow genome and, similar to previous studies, we found a large amount of novel variations. Better knowledge of these variations could explain significant phenotypic differences (e.g., health, production, reproduction) between different breeds.

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Sequencing and annotated analysis of an Estonian human genome

Cited by 4 publications

References 22 publications

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

The sequencing and interpretation of the genome obtained from a Serbian individual

Sequencing and annotated analysis of the Holstein cow genome

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