Pub Date : 2023-01-01DOI: 10.23937/2378-3648/1410054
Liao Zhencheng, Ye Fan, Tao Ying, W. Jun, Huang Guan, Yang Siyi, Lu Zhaoqun, Zhu Honglei, Wu Pingan
{"title":"m6A Demethylase FTO Regulates Nasopharyngeal Carcinoma Invasion, Migration","authors":"Liao Zhencheng, Ye Fan, Tao Ying, W. Jun, Huang Guan, Yang Siyi, Lu Zhaoqun, Zhu Honglei, Wu Pingan","doi":"10.23937/2378-3648/1410054","DOIUrl":"https://doi.org/10.23937/2378-3648/1410054","url":null,"abstract":"","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68748611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-28DOI: 10.23937/2378-3648/1410045
Silva Kleber Santiago Freitas e
RAD51a is a highly conserved protein and its major role is the repair of DNA double strand breaks. Endogenous species are generated during normal cell metabolic activities and can cause damage to DNA, as well as several environmental factors. The interactions RAD51a perform with other proteins help the maintenance of oncogenetic metabolism within cells. RAD51a interacts with PCNA, FANCD2 and ABL1, among many other cancer-related proteins. PCNA acts as a DNA clamp and is related to the replication process, FANCD2 arrests DNA replication fork progression in response to DNA damage and ABL1 is a proto-oncogene related to cell differentiation. Protein-protein interactions (PPIs) are governed by the presence of hot spots within the interface of interaction. Identifying residues directly involved in PPIs enables the likelihood of modulating such complexes with biologically active small molecules such as synthetic peptides, which leads to a new era of diseases treatment. Here, we use an in silico approach to determine the best free-energy of interaction between RAD51a and the targeted cancer-related proteins PCNA, FANCD2 and two chains of ABL1. We propose an interaction interface between RAD51a and those proteins and identified hot spots that could be useful to understand the molecular basis of their interaction. We believe that further studies may find small-targeted molecules with therapeutics properties that could modulate those interactions and increase our knowledge regarding the complex trait diseases such as cancer.
{"title":"In silico Characterization of Rad51a Interactions with Cancer-Related Proteins","authors":"Silva Kleber Santiago Freitas e","doi":"10.23937/2378-3648/1410045","DOIUrl":"https://doi.org/10.23937/2378-3648/1410045","url":null,"abstract":"RAD51a is a highly conserved protein and its major role is the repair of DNA double strand breaks. Endogenous species are generated during normal cell metabolic activities and can cause damage to DNA, as well as several environmental factors. The interactions RAD51a perform with other proteins help the maintenance of oncogenetic metabolism within cells. RAD51a interacts with PCNA, FANCD2 and ABL1, among many other cancer-related proteins. PCNA acts as a DNA clamp and is related to the replication process, FANCD2 arrests DNA replication fork progression in response to DNA damage and ABL1 is a proto-oncogene related to cell differentiation. Protein-protein interactions (PPIs) are governed by the presence of hot spots within the interface of interaction. Identifying residues directly involved in PPIs enables the likelihood of modulating such complexes with biologically active small molecules such as synthetic peptides, which leads to a new era of diseases treatment. Here, we use an in silico approach to determine the best free-energy of interaction between RAD51a and the targeted cancer-related proteins PCNA, FANCD2 and two chains of ABL1. We propose an interaction interface between RAD51a and those proteins and identified hot spots that could be useful to understand the molecular basis of their interaction. We believe that further studies may find small-targeted molecules with therapeutics properties that could modulate those interactions and increase our knowledge regarding the complex trait diseases such as cancer.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43892963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-18DOI: 10.23937/2378-3648/1410043
A. Shahin
TAR syndrome is a genetic disorder characterized by a lack of radial bone in the forearm and a lack of blood platelets. Thrombocytopenia prevents normal blood clotting and causes bleeding easily and often bleeds from the nose. The TAR syndrome is caused by the mutation of the RBM8A gene, which is based on the long arm of chromosome 1, which is based on 1q21.1.
{"title":"The Role of Genetic Mutations in Gene RBM8A in Thrombocytopenia-Absent Radius Syndrome","authors":"A. Shahin","doi":"10.23937/2378-3648/1410043","DOIUrl":"https://doi.org/10.23937/2378-3648/1410043","url":null,"abstract":"TAR syndrome is a genetic disorder characterized by a lack of radial bone in the forearm and a lack of blood platelets. Thrombocytopenia prevents normal blood clotting and causes bleeding easily and often bleeds from the nose. The TAR syndrome is caused by the mutation of the RBM8A gene, which is based on the long arm of chromosome 1, which is based on 1q21.1.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49474486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.23937/2378-3648/1410047
OB Bassey, L. Chukwu, GC Alimba
Pollution of aquatic ecosystems from anthropogenic activities has heightened in recent times and this has elicited national and international concern on the impacts on aquatic biota. This study investigated the genotoxic effects in C. nigrodigitatus from two polluted lagoons. Micronuclei (MN) test, as an index of chromosomal damage, is widely applied in field studies. The peripheral erythrocytes from C. nigrodigitatus were subjected to MN analysis and physicochemical parameters were evaluated following APHA standardized protocol. There were significant (p < 0.05) seasonal variations in water temperature, pH, dissolved oxygen (DO) and biochemical oxygen demand (BOD5) across sampling stations in both lagoons. The levels of DO and BOD5 were below permissible limits (FMEnv) in both lagoons. Cytogenetic analyses revealed a statistically significant (p < 0.05) in MN frequencies with 70.2% and 29.8%, while the nuclear abnormalities (NAs) observed an increased formation of 68.7% Binucleated cells (BN) and 31.3% BN; 60% of blebbed cells (BL) and 40% BL; 58.8% lobed cell (LB) and 41.2% LB in Ologe and Badagry lagoons respectively. MN and NAs induction increased in the order of frequencies; MN > BN > BL > LB in the peripheral erythrocyte of catfish from both lagoons. Pearson correlation showed negative significant induction (p < 0.05) with the frequencies of MN and BN induced by BOD and Conductivity in both lagoons. The induction of MN formation and nuclear abnormalities (NAs) in catfish are sensitive non-specific indicators for mutagenic damage, exposed to admixtures of chemical and organic compounds from Ologe and Badagry lagoons. Thus, micronucleus assay serves as a good biomarker for biomonitoring aquatic ecosystems.
{"title":"Cytogenetics of Chrysichthys nigrodigitatus as Bioindicator of Environmental Pollution from Two Polluted Lagoons, South-Western Nigeria","authors":"OB Bassey, L. Chukwu, GC Alimba","doi":"10.23937/2378-3648/1410047","DOIUrl":"https://doi.org/10.23937/2378-3648/1410047","url":null,"abstract":"Pollution of aquatic ecosystems from anthropogenic activities has heightened in recent times and this has elicited national and international concern on the impacts on aquatic biota. This study investigated the genotoxic effects in C. nigrodigitatus from two polluted lagoons. Micronuclei (MN) test, as an index of chromosomal damage, is widely applied in field studies. The peripheral erythrocytes from C. nigrodigitatus were subjected to MN analysis and physicochemical parameters were evaluated following APHA standardized protocol. There were significant (p < 0.05) seasonal variations in water temperature, pH, dissolved oxygen (DO) and biochemical oxygen demand (BOD5) across sampling stations in both lagoons. The levels of DO and BOD5 were below permissible limits (FMEnv) in both lagoons. Cytogenetic analyses revealed a statistically significant (p < 0.05) in MN frequencies with 70.2% and 29.8%, while the nuclear abnormalities (NAs) observed an increased formation of 68.7% Binucleated cells (BN) and 31.3% BN; 60% of blebbed cells (BL) and 40% BL; 58.8% lobed cell (LB) and 41.2% LB in Ologe and Badagry lagoons respectively. MN and NAs induction increased in the order of frequencies; MN > BN > BL > LB in the peripheral erythrocyte of catfish from both lagoons. Pearson correlation showed negative significant induction (p < 0.05) with the frequencies of MN and BN induced by BOD and Conductivity in both lagoons. The induction of MN formation and nuclear abnormalities (NAs) in catfish are sensitive non-specific indicators for mutagenic damage, exposed to admixtures of chemical and organic compounds from Ologe and Badagry lagoons. Thus, micronucleus assay serves as a good biomarker for biomonitoring aquatic ecosystems.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68748547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-31DOI: 10.23937/2378-3648/1410040
M. E. Fernandez-de-Cossio, A. Cintado, M. Nazábal, H. Camacho, T. Díaz, A. Villarreal, M. Ale, D. Grass, M. Cervantes‐Llanos, N. Pavón‐Fuentes, J. Benítez, J. Cabrera-Gómez, A. Fe, G. Pentón-Rol
Background: Neuromyelitis optica (NMO) is a complex immune-mediated disease whose prevalence differs among ethnic groups, most likely due to genetic factors. The presence of the Human Leucocyte Antigens (HLA) extended haplotype is a risk for NMO. The tumor necrosis factor-alpha (TNF-a) is believed to play a role in NMO pathogenesis. Although single nucleotide polymorphisms (SNPs) in the TNF-a promoter region (pTNF-a) has been shown to influence levels of TNF-a production, such an association is not evident in the Cuban population. The aim of this study was to examine the association between the HLA alleles, pTNF-a SNPs, the amount of the TNF-a protein, and the clinical parameters of a sample of NMO patients from the Cuban population. Methods: 20 patients diagnosed with relapsing NMO (R-NMO), and 100 unrelated healthy controls, were evaluated. Ancestry was determined and an HLA typing case-control association study was carried out. Genomic DNA was extracted from peripheral blood leucocytes. HLA DRB1 and DQ alleles typing were determined by SSP-PCR. The DNA sequence approach was used to evaluate pTNF-a SNPs. The TNF-a protein expression was measured by ELISA. Results: Genetic ancestry estimates showed that in NMO patients the European contribution prevailed. No association of HLA alleles to NMO susceptibility was observed, although there was a slight protective effect of HLA DQA*03, DRB1*10 followed by DRB1*11 alleles. An association was found between the pTNF-a 308 G/A and a possible protective role against NMO (OR = 0.37, p values p < 0.001). The TNF-a protein did not differ between NMO patients and controls. Moreover, the association of HLA alleles and SNPs was not statistically significant when the clinical parameter were evaluated. Conclusion: Our results showed that in this sample of Cuban NMO patients HLA alleles as well as pTNF-a SNPs differ from other populations. There was no association between HLA alleles, pTNF-a SNPs and clinical variables.
{"title":"HLA DRB1*/DQA1*Alleles and TNF-alpha G308A Polymorphism Protect against Neuromyelitis Optica in the Cuban Population","authors":"M. E. Fernandez-de-Cossio, A. Cintado, M. Nazábal, H. Camacho, T. Díaz, A. Villarreal, M. Ale, D. Grass, M. Cervantes‐Llanos, N. Pavón‐Fuentes, J. Benítez, J. Cabrera-Gómez, A. Fe, G. Pentón-Rol","doi":"10.23937/2378-3648/1410040","DOIUrl":"https://doi.org/10.23937/2378-3648/1410040","url":null,"abstract":"Background: Neuromyelitis optica (NMO) is a complex immune-mediated disease whose prevalence differs among ethnic groups, most likely due to genetic factors. The presence of the Human Leucocyte Antigens (HLA) extended haplotype is a risk for NMO. The tumor necrosis factor-alpha (TNF-a) is believed to play a role in NMO pathogenesis. Although single nucleotide polymorphisms (SNPs) in the TNF-a promoter region (pTNF-a) has been shown to influence levels of TNF-a production, such an association is not evident in the Cuban population. The aim of this study was to examine the association between the HLA alleles, pTNF-a SNPs, the amount of the TNF-a protein, and the clinical parameters of a sample of NMO patients from the Cuban population. Methods: 20 patients diagnosed with relapsing NMO (R-NMO), and 100 unrelated healthy controls, were evaluated. Ancestry was determined and an HLA typing case-control association study was carried out. Genomic DNA was extracted from peripheral blood leucocytes. HLA DRB1 and DQ alleles typing were determined by SSP-PCR. The DNA sequence approach was used to evaluate pTNF-a SNPs. The TNF-a protein expression was measured by ELISA. Results: Genetic ancestry estimates showed that in NMO patients the European contribution prevailed. No association of HLA alleles to NMO susceptibility was observed, although there was a slight protective effect of HLA DQA*03, DRB1*10 followed by DRB1*11 alleles. An association was found between the pTNF-a 308 G/A and a possible protective role against NMO (OR = 0.37, p values p < 0.001). The TNF-a protein did not differ between NMO patients and controls. Moreover, the association of HLA alleles and SNPs was not statistically significant when the clinical parameter were evaluated. Conclusion: Our results showed that in this sample of Cuban NMO patients HLA alleles as well as pTNF-a SNPs differ from other populations. There was no association between HLA alleles, pTNF-a SNPs and clinical variables.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46290259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-31DOI: 10.23937/2378-3648/1410036
P. Padmanabhan, Nagesh Srikakulam, K. Kumar, J. Christdas, G. Pandi
Abelmoschus esculentus is widely cultivated and consumed across the globe for its nutritional and medicinal purpose. In spite of the growing demand, its cultivation is massively affected by various insects, fungi, nematodes and viruses. Due to lack of genomic and limited transcriptomic resources, genetic manipulation studies concerning the crop improvement against various environmental factors is scarce for this crop. Thereby, the present study aims to develop high quality transcriptome of A. esculentus by employing the Next-Generation based RNA sequencing of four cDNA libraries generated from the leaf samples. Sequencing yielded a total of 206.3 million paired-end clean reads with 66,382 assembled unigenes having a total length of 71.35 Mb, an average length of 1,074 bp and an N50 of 1,408 bp. About 56% of the unigenes were successfully annotated in four public databases including Pfam, GO, COG, and KEGG. GO analysis revealed that the majority of the annotated unigenes were involved in key biological processes like ATP binding, DNA binding, transcription, DNA-templated, and integral component of membrane. KEGG pathway analysis showed that 16,307 unigenes were assigned to 143 pathways in which majority of secondary metabolites related transcripts involving in phenylpropanoids, flavonoid and terpenoid biosynthesis pathway were identified. In addition, transcription factor and simple sequence repeats (SSRs) analyses revealed 76 transcription factor families and 9,578 potential SSRs in the A. esculentus leaf transcriptome. Furthermore, de novo assembled leaf transcriptome generated in the present study had longer transcripts with better N50 sizes and the quality of assembly was ensured by qRT-PCR analysis. The A. esculentus sequence information presented in this study will be a valuable resource for further molecular genetics and functional genomics studies for the improvement of this crop plant.
{"title":"Comprehensive Leaf Transcriptome of a Non-model Plant, Abelmoschus esculentus for the Functional Genomics Studies","authors":"P. Padmanabhan, Nagesh Srikakulam, K. Kumar, J. Christdas, G. Pandi","doi":"10.23937/2378-3648/1410036","DOIUrl":"https://doi.org/10.23937/2378-3648/1410036","url":null,"abstract":"Abelmoschus esculentus is widely cultivated and consumed across the globe for its nutritional and medicinal purpose. In spite of the growing demand, its cultivation is massively affected by various insects, fungi, nematodes and viruses. Due to lack of genomic and limited transcriptomic resources, genetic manipulation studies concerning the crop improvement against various environmental factors is scarce for this crop. Thereby, the present study aims to develop high quality transcriptome of A. esculentus by employing the Next-Generation based RNA sequencing of four cDNA libraries generated from the leaf samples. Sequencing yielded a total of 206.3 million paired-end clean reads with 66,382 assembled unigenes having a total length of 71.35 Mb, an average length of 1,074 bp and an N50 of 1,408 bp. About 56% of the unigenes were successfully annotated in four public databases including Pfam, GO, COG, and KEGG. GO analysis revealed that the majority of the annotated unigenes were involved in key biological processes like ATP binding, DNA binding, transcription, DNA-templated, and integral component of membrane. KEGG pathway analysis showed that 16,307 unigenes were assigned to 143 pathways in which majority of secondary metabolites related transcripts involving in phenylpropanoids, flavonoid and terpenoid biosynthesis pathway were identified. In addition, transcription factor and simple sequence repeats (SSRs) analyses revealed 76 transcription factor families and 9,578 potential SSRs in the A. esculentus leaf transcriptome. Furthermore, de novo assembled leaf transcriptome generated in the present study had longer transcripts with better N50 sizes and the quality of assembly was ensured by qRT-PCR analysis. The A. esculentus sequence information presented in this study will be a valuable resource for further molecular genetics and functional genomics studies for the improvement of this crop plant.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48811750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-31DOI: 10.23937/2378-3648/1410033
Zinatizadeh Mohammad Reza, Masoumalinejad Zahra, N. Azim, Shekari Mohammad, Parnak Farzaneh, Zaree Faeghe
NF-κB essential modulator (NEMO) syndrome is an immunodeficiency disease. NF-κB proteins, which regulate the expression of genes that moderate important physiological processes, are called regulatory of cell homeostasis. NEMO is a protein in the IKK inhibitor complex that many organ systems normally do not grow. Cells (as well as organ and tissues) do not grow proteins they express proteins. The disease occurs due to mutation in the IKBKG gene. The IKBKG gene, located in the Xq28 chromosomal region or located in the X chromosome. The disease indicates an impairment of NF-κB activation and the initial treatment of NEMO is very difficult. About 70-80% of patients have similar DNA rearrangements. Epilepsy is observed in about 50% of patients with these disorders. Therefore, there is little information about the NEMO disease and more research is needed to further examine the syndrome.
{"title":"A Review of NEMO Protein and its Relationship with Genetic Diseases","authors":"Zinatizadeh Mohammad Reza, Masoumalinejad Zahra, N. Azim, Shekari Mohammad, Parnak Farzaneh, Zaree Faeghe","doi":"10.23937/2378-3648/1410033","DOIUrl":"https://doi.org/10.23937/2378-3648/1410033","url":null,"abstract":"NF-κB essential modulator (NEMO) syndrome is an immunodeficiency disease. NF-κB proteins, which regulate the expression of genes that moderate important physiological processes, are called regulatory of cell homeostasis. NEMO is a protein in the IKK inhibitor complex that many organ systems normally do not grow. Cells (as well as organ and tissues) do not grow proteins they express proteins. The disease occurs due to mutation in the IKBKG gene. The IKBKG gene, located in the Xq28 chromosomal region or located in the X chromosome. The disease indicates an impairment of NF-κB activation and the initial treatment of NEMO is very difficult. About 70-80% of patients have similar DNA rearrangements. Epilepsy is observed in about 50% of patients with these disorders. Therefore, there is little information about the NEMO disease and more research is needed to further examine the syndrome.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41459982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-31DOI: 10.23937/2378-3648/1410041
B. Mark, Bayer Philipp E, Daal Angela van
There is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. Despite intensive research on the genetics of craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. As a part of efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a targeted candidate gene approach by selecting 1,319 single nucleotide polymorphisms (SNPs) in over 170 candidate genes and intergenic regions. This list has been further expanded with additional 4,732 tag polymorphisms, representing extended haplotype. All the markers were genotyped in 587 DNA samples using a massively parallel sequencing approach. We used 3-dimentional (3D) facial scans and direct cranial measurements to calculate 104 craniofacial anthropometric distances, which were analysed for associations with 2,332 polymorphisms. An application of a Bonferroni corrected genome wide significance threshold produced associations between six SNPs and five craniofacial traits. Specifically, significant associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and a composite trait represented by a principal component with rs37369 (5p13.2) and rs390345 (14q31.3) were observed. Due to over-conservative nature of the Bonferroni correction, we also report the associations that reached the traditional genome-wide p-value threshold (< 5.00E-08) as suggestive. Based on the genome-wide significance threshold, 8 craniofacial phenotypes demonstrated significant and mostly novel associations with 33 intergenic and extragenic SNPs, potentially involved in gene regulation. This study identified a large number of genetic variants associated with normal craniofacial morphology variation, including confirmation of the two previously reported genes. These results enhance our understanding of the craniofacial genetics affecting normal craniofacial appearance and will be of particular value for clinical diagnostics and forensic molecular phenotyping.
{"title":"Identification of the Single Nucleotide Polymorphisms Affecting Normal Phenotypic Variability in Human Craniofacial Morphology Using Candidate Gene Approach","authors":"B. Mark, Bayer Philipp E, Daal Angela van","doi":"10.23937/2378-3648/1410041","DOIUrl":"https://doi.org/10.23937/2378-3648/1410041","url":null,"abstract":"There is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. Despite intensive research on the genetics of craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. As a part of efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a targeted candidate gene approach by selecting 1,319 single nucleotide polymorphisms (SNPs) in over 170 candidate genes and intergenic regions. This list has been further expanded with additional 4,732 tag polymorphisms, representing extended haplotype. All the markers were genotyped in 587 DNA samples using a massively parallel sequencing approach. We used 3-dimentional (3D) facial scans and direct cranial measurements to calculate 104 craniofacial anthropometric distances, which were analysed for associations with 2,332 polymorphisms. An application of a Bonferroni corrected genome wide significance threshold produced associations between six SNPs and five craniofacial traits. Specifically, significant associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and a composite trait represented by a principal component with rs37369 (5p13.2) and rs390345 (14q31.3) were observed. Due to over-conservative nature of the Bonferroni correction, we also report the associations that reached the traditional genome-wide p-value threshold (< 5.00E-08) as suggestive. Based on the genome-wide significance threshold, 8 craniofacial phenotypes demonstrated significant and mostly novel associations with 33 intergenic and extragenic SNPs, potentially involved in gene regulation. This study identified a large number of genetic variants associated with normal craniofacial morphology variation, including confirmation of the two previously reported genes. These results enhance our understanding of the craniofacial genetics affecting normal craniofacial appearance and will be of particular value for clinical diagnostics and forensic molecular phenotyping.","PeriodicalId":91313,"journal":{"name":"Journal of genetics and genome research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41527511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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