Лонгитюдные генетические исследования когнитивных характеристик

Рассмотрена роль лонгитюдных исследований когнитивных характеристик в определении причин, влияющих на познание, с целью возможной их коррекции для улучшения познавательных навыков. В данных исследованиях показано, что на развитие когнитивных функций влияют такие средовые факторы, как качество нутриентов, стресс во время гестации и характер социального окружения. Выявлены специфические эпигенетические изменения, выступающие в качестве посредников между генотипом и средой в реализации когнитивных функций. В связи с важным значением эпигенома перспективна разработка методов терапии когнитивных расстройств с использованием агентов, влияющих на метилирование и модификации гистонов. Развивающимся направлением в этой области является изучение некодирующих РНК, которые способны модифицировать эпигенетические факторы. За последние годы проведены широкомасштабные метаанализы результатов исследований роли генетических ассоциаций с различными когнитивными характеристиками. Показано значение активно экспрессирующихся в головном мозге генов, таких как BDNF, COMT, CADM2, CYP2D6, APBA1, CHRNA7, PDE1C, PDE4B, PDE4D. С физиологическим познанием оказались ассоциированы гены, вовлеченные в развитие психических заболеваний (MEF2C, CYP2D6, FAM109B, SEPT3, NAGA, TCF20, NDUFA6). В развитие психических заболеваний с когнитивным дефицитом вовлечены гены, участвующие в метилировании ДНК (DNMT1, DNMT3B, FTO), модификации гистонов (CREBBP, CUL4B, EHMT1, EP300, EZH2, HLCS, HUWE1, KAT6B, KMT2A, KMT2D, KMT2C, NSD1, WHSC1, UBE2A) и моделировании хроматина (ACTB, ARID1A, ARID1B, ATRX, CHD2, CHD7, CHD8, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SRCAP, SS18L1), которые имеют значение в регуляции когнитивных функций у здоровых людей. Приведены данные, позволяющие предположить, что трансгенерационное наследование когнитивных характеристик связано с некодирующими РНК, а также со способностью мобильных элементов, инсертированных в межгенные области, влиять на регуляцию функционирующих в головном мозге генов за счет процессинга транскриптов транспозо-нов в некодирующие РНК. Особенности состава, количества и распределения в геноме мобильных элементов, которые не изменяют нуклеотидные последовательности белок-кодирующих генов, но влияют на их экспрессию, могут передаваться из поколения в поколение.

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