The detailed investigation of varia

The detailed investigation of variation in functionally important regions of the human genome is expected to
promote understanding of genetically complex diseases. We resequenced 65 candidate genes for CNS disorders in an
average of 85 European individuals. The minor allele frequency (MAF), an indicator of weak purifying selection, was
lowest in radical amino acid alterations, whereas similar MAF was observed for synonymous variants and
conservative amino acid alterations. In noncoding sequences, variants located in CpG islands tended to have a lower
MAF than those outside CpG islands. The transition/transversion ratio was increased among both synonymous and
conservative variants compared with noncoding variants. Conversely, the transition/transversion ratio was lowest
among radical amino acid alterations. Furthermore, among nonsynonymous variants, transversions displayed lower
MAF than did transitions. This suggests that transversions are associated with functionally important amino acid
alterations. By comparing our data with public SNP databases, we found that variants with lower allele frequency are
underrepresented in these databases. Therefore, radical variants obtain distinctively lower database coverage.
However, those variants appear to be under weak purifying selection and thus could play a role in the etiology of
genetically complex diseases.

Results (Indonesian) 1:

Penyelidikan rinci dari variasi di fungsional penting daerah genom manusia diharapkanmempromosikan pemahaman penyakit genetik kompleks. Kami resequenced 65 calon gen untuk gangguan SSP dirata-rata orang Eropa 85. Frekuensi alel kecil (MAF), indikator lemah memurnikan seleksi,terendah di perubahan radikal asam amino, sedangkan serupa MAF diamati untuk varian identik danperubahan konservatif asam amino. Dalam urutan noncoding, varian terletak di pulau-pulau CpG cenderung memiliki lebih rendahMAF daripada orang-orang di luar Kepulauan CpG. Transisi transversion rasio meningkat diantara keduanya identik danvarian konservatif dibandingkan dengan varian noncoding. Sebaliknya, rasio transisi transversion adalah terendahdi antara perubahan radikal asam amino. Selain itu, antara nonsynonymous varian, transversions ditampilkan lebih rendahMAF daripada transisi. Hal ini menunjukkan bahwa transversions berhubungan dengan fungsional penting asam aminoperubahan. Dengan membandingkan data kami dengan umum SNP database, kita menemukan bahwa varian dengan Frekuensi alel yang lebih rendahyang kurang terwakili di database ini. Oleh karena itu, varian radikal memperoleh khas lebih rendah database cakupan.Namun, varian yang muncul untuk menjadi di bawah pilihan memurnikan lemah dan dengan demikian dapat memainkan peran dalam penyebabpenyakit genetik kompleks.