Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Minisatellite 5 of SLC6A18 (SLC6A18-MS5): Relationship to Hypertension and Evolutional Level

SLC6A18 유전자의 minisatellites 5 (SLC6A18-MS5)의 고혈압과의 관련성 및 진화적 의미

  • 허창환 (동아대학교 자연과학대학 생명과학과) ;
  • 이상엽 (동아대학교 자연과학대학 생명과학과) ;
  • 설소영 (동아대학교 자연과학대학 생명과학과) ;
  • 권정아 (동아대학교 자연과학대학 생명과학과) ;
  • 정윤희 (동아대학교 자연과학대학 생명과학과) ;
  • 정정남 (동아대학교 자연과학대학 생명과학과) ;
  • 선우양일 (동아대학교 자연과학대학 생명과학과)
  • Published : 2008.12.30
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Abstract

SLC6A18, one of the neurotransmitters, was reported the possible relationship to hypertension, and it contained eight blocks of minisatellites. In this study, SLC6A18-MS5 sequence which showed the highest heterozygosity among seven minisatellites was analyzed using the Transfac software, the putative binding sites for the transcription factor Pax4 and HNF4 were discovered as a result. The HNF4 is involved in the diabetes pathway and suggested the relationship to hypertension. Thus, we investigated the putative functional significance of allelic variation in this minisatellites with respect to susceptibility for hypertension. To address this possibility, we analyzed genomic DNA from the blood of 301 hypertension-free controls and 184 cases with hypertension. A statistically significant association was not identified between the allelic distribution of SLC6A18-MS5 and occurrence of hypertension. We then examined the meiotic segregation of SLC6A18-MS5 and it was transmitted following Mendelian inheritance. Therefore, this locus could be useful markers for paternity mapping and DNA fingerprinting. Moreover, we undertook a comprehensive analysis of the genomic sequence to address the evolutionary events of these variable repeats. SLC6A18 minisatellites regions are only conserved in human and primates. This result suggestedthat intronic minisatellites analysis is powerful evolution marker for the non-coding regions in primates and can provide a great insight to the molecular evolution of repeated region in primates.

SLC6A18은 neurotransmitter로서 고혈압과 연관성이 보고 되었고, 유전자 내에 총 8개의 minisatellites가 존재함이 밝혀졌다. 본 연구에서 8개 minisatellites 중 가장 높은 heterozygosity를 나타내는 SLC6A18-MS5 영역에 대하여 생물정보학적 방법으로 Transfac software를 이용하여 transcription factor binding site를 분석한 결과, Pax4와 HNF4의 binding site를 발견하였다. HNF4는 당뇨병 대사에 관여하는 것으로 고혈압과의 연관성이 있을 것으로 사료된다. 그러므로 본 연구에서는 SLC6A18-MS5 영역과 고혈압과의 연관성을 조사하기 위하여, 대조군 301명과 고혈압 환자군 184명의 genomic DNA를 이용하여 대립형질의 패턴을 조사하였다. SLC6A18-MS5의 대립형질 분포와 고혈압은 직접적인 영향을 주지 않는 것으로 나타났다. 반면 높은 heterozygosity를 나타내는 SLC6A18-MS5에 친자확인 및 DNA typing 마커로서의 유용성을 알아보기 위해 20가족의 샘플을 이용하여, 감수분열 후 자손에의 분리 형태를 조사한 결과 부모에게서 자손으로 정확히 전달되는 멘델의 법칙에 의해 분리됨을 확인하였다. 또한 SLC6A18 유전자 내의 minisatellites들의 진화적 관계를 조사한 결과, 인간과 원숭이에서만 보존적으로 나타났다. 이러한 결과는 intron영역의 minisatellites 분석이 영장류의 비암호화 영역의 중요한 진화 마커로 사용될 수 있음을 나타내어, 영장류 특이적 진화를 이해하는데 도움이 될 것으로 사료된다.

Keywords

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