Импутация генотипов в геномных исследованиях человека

Импутация – это метод, позволяющий восстанавливать недостающую информацию о генетических вариантах, которые не удалось генотипировать напрямую с помощью ДНК-микрочипов или секвенирования с низким покрытием. Импутация играет важнейшую роль в полногеномном анализе ассоциаций (genome wide associations study, GWAS). Она приводит к существенному увеличению количества изучаемых вариантов, что повышает разрешающую способность метода и увеличивает сопоставимость данных, полученных в разных когортах и/или с помощью разных технологий, что важно при проведении метаанализов. При ее выполнении информацию о генотипах в исследуемой выборке, у которой известна только часть генетических вариантов, дополняют за счет эталонной (референсной) выборки, имеющей более полные данные о генотипах (чаще всего это результаты полногеномного секвенирования). Импутация стала неотъемлемой частью геномных исследований человека благодаря преимуществам, которые она дает, а также увеличению доступности инструментов для импутации и данных референсных выборок. Обзор посвящен импутации в геномных исследованиях человека. В первом разделе приводятся описание технологий получения информации о генотипах человека и характеристика получаемых типов данных. Во втором разделе представлена методология импутации, перечисляются этапы ее проведения и соответствующие программы, дается описание наиболее популярных референсных панелей и способов оценки качества импутации. В заключении представлены примеры использования импутации в геномных исследованиях выборок из России. Настоящий обзор показывает важность проведения импутации, дает информацию о том, как ее выполнять, и систематизирует результаты ее применения на примере российских выборок. 

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