Популяционная генетика полиглутаминовых спиноцеребеллярных атаксий

Наследственные заболевания нервной системы – одна из наиболее актуальных проблем медицины XXI века. Особо выделяются те, которые доминируют в этой группе. К таким заболеваниям, безусловно, можно отнести полиглутаминовые спиноцеребеллярные атаксии (СЦА), имеющие в своей основе молекулярные механизмы быстро прогрессирующей экспансии среди различных групп населения нашей планеты. Это СЦА1, 2, 3, 6, 7 и 17, фенотипически объединенные в одну группу по принципу развития мозжечковой атаксии вследствие специфических генетических причин. Субстратом данных генетических заболеваний является ЦАГ тринуклеотидная последовательность (цитозин-аденин-гуанин), которая имеет тенденцию к увеличению при передаче генома последующим поколениям. Поэтому характерная особенность этих заболеваний – не только количественное увеличение больных, но и качественное изменение течения их неврологической симптоматики. Все это отражается в структуре заболеваемости полиглутаминовыми СЦА как на глобальном общемировом уровне, так и на уровне отдельных групп населения конкретных регионов. Однако большинство работ, посвященных популяционной генетике полиглутаминовых СЦА, ограничиваются количественными показателями конкретной нозологии на определенной территории, тогда как история возникновения и принципы распространения полиглутаминовых СЦА на сегодняшний день исследованы недостаточно хорошо. Это не позволяет делать долгосрочные прогнозы относительно динамики в последующих поколениях и управлять мутагенным процессом. В настоящей работе представлен детальный анализ популяционной генетики полиглутаминовых СЦА, выведены общие генетические и частные закономерности их развития и особенности популяционной динамики в мире и в Российской Федерации. Обозначены проблемы в исследовании и выявлении таких заболеваний. Для лучшего понимания необходимо охватить широкий пласт популяций Африки, Азии и Южной Америки, что будет возможно при развитии новых методов молекулярной генетики. Такой подход к исследованию полиглутаминовых СЦА позволяет обозначить их место в контексте генетических заболеваний головного мозга и определить особенности распространения и методов генетической профилактики.

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