Merlin Butler

Publications (125) View all

• Article: Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

  Douglas Bittel, Merlin Butler, Nataliya Kibiryeva, Jennifer Marshall, Jie Chen, Gary Lofland, James O&apos, Brien
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  ABSTRACT: Abstract Background Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot. Methods We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects. Results We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003) appeared to be generally suppressed. Conclusions The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.
  BMC Medical Genomics. 01/2011;
• Article: Apo lipoprotein A1 gene polymorphisms predict cardio-metabolic risk in South Asian immigrants.

  Sunita Dodani, Rebecca Henkhaus, Lei Dong, Merlin G Butler
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  ABSTRACT: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL). A community-based study on South Asians aged 35--65 years without CAD was conducted. APOA1 gene sequencing was performed and genotypes compared with cardiovascular findings. The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novel APOA1 gene single nucleotide peptides ({SNPs}) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037). APOA1 gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations of APOA1 SNPs with metabolic syndrome and low HDL remained after age-adjustment. Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.
  Disease markers 01/2012; 32(1):9-19. · 1.64 Impact Factor
• Article: 14q32 deletion syndrome: a clinical report.

  Erin L Youngs, Majed Dasouki, Merlin G Butler
  Clinical dysmorphology 01/2012; 21(1):42-4. · 0.47 Impact Factor
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  Article: 12-year-old boy with a 4q35.2 microdeletion and involvement of MTNR1A, FAT1, and F11 genes.

  Erin L Youngs, Rebecca S Henkhaus, Jessica A Hellings, Merlin G Butler
  Clinical dysmorphology 11/2011; 21(2):93-6. · 0.47 Impact Factor
• Article: Methylation-specific multiplex ligation-dependent probe amplification and identification of deletion genetic subtypes in Prader-Willi syndrome.

  Rebecca S Henkhaus, Soo-Jeong Kim, Virginia E Kimonis, June-Anne Gold, Elisabeth M Dykens, Daniel J Driscoll, Merlin G Butler
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  ABSTRACT: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are complex neurodevelopmental disorders caused by loss of expression of imprinted genes from the 15q11-q13 region depending on the parent of origin. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) kits from MRC-Holland (Amsterdam, The Netherlands) were used to detect PWS and AS deletion subtypes. We report our experience with two versions of the MS-MLPA-PWS/AS kit (original A1 and newer B1) in determining methylation status and deletion subtypes in individuals with PWS. MS-MLPA analysis was performed on DNA isolated from a large cohort of PWS subjects with the MS-MLPA-PWS/AS-A1 and -B1 probe sets. Both MS-MLPA kits will identify deletions in the 15q11-q13 region but the original MS-MLPA-A1 kit has a higher density of probes at the telomeric end of the 15q11-q13 region, which is more useful for identifying individuals with atypical deletions. The newer B1 kit contains more probes in the imprinting center (IC) and adjoining small noncoding RNAs useful in identifying small microdeletions. The A1 kit identified the typical deletions and smaller atypical deletions, whereas the B1 kit was more informative for identifying microdeletions including the IC and SNORD116 regions. Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions.
  Genetic Testing and Molecular Biomarkers 10/2011; 16(3):178-86. · 1.11 Impact Factor