F. de Medicina de Petrópolis – FMP 2022: Inglês

Texto

Origins of mutation

Computational analysis reveals sources of genetic variations

The precise transmission of genetic information from one generation to the next is fundamental to life. Most of the time, this process unfolds with remarkable accuracy, but when it goes wrong, mutations can arise – some of them beneficial, some of them inconsequential, and some of them causing malfunction and disease.

Yet, precisely where and how heritable genetic mutations tend to arise in humans has remained largely unknown.

Now, a new multi-institutional study led by investigators at Harvard Medical School and Brigham and Women's Hospital has detected nine processes during which most human genetic mutations tend to arise.

The work, published on Aug. 12 in Science, is based on an analysis of 400 million rare DNA human variants and represents one of the most comprehensive computational efforts to explore heritable genomic variations.

"Genetic mutations are a rare yet inevitable and, indeed essential, part of the development and propagation of the human species – they create genetic diversity, fuel evolution, and occasionally cause genetic diseases," said study lead investigator Shamil Sunyaev, professor of biomedical informatics in the Blavatnik Institute at HMS and professor of medicine at Brigham and Women's.

"Connecting the power of computation and big data, we analyzed genomic variations and identified a set of biologic processes responsible for the vast majority of heritable human mutations," added Sunyaev, who conducted the work with lead authors Vladimir Seplyarskiy, HMS research fellow in medicine at Brigham and Women's, and Ruslan Soldatov, instructor in biomedical informatics at HMS.

The research identified new mutation-fueling mechanisms and some that were already known. One mechanism was related to inaccurate copying of DNA, another was related to chemical damage occurring to the DNA. The analysis also detected a machinery involved in human gene regulation as a frequent malefactor in mutations. This machinery is particularly active during early embryonic development, and most of the mutations introduced by the machinery occur during this period. In one surprising finding, the researchers identified a mutation-driving mechanism that was not related to DNA copying and cellular division – processes that are predisposed to mutation-causing anomalies. This previously unsuspected mechanism leads to mutations in egg cells stored in the ovaries.

The researchers are now working to incorporate some of the results in a model of human-mutation rate along the genome in an effort to help predict the chance that a specific mutation would occur at a specific location in the genome. The goal is to help in the analysis of disease mutations and in discovery of genes causing rare diseases. The model may also serve to highlight genes of key importance to human health and survival.

Available at: <https: //www.sciencedaily.com/releases/2021/

08/210813100335.htm>. Retrieved on: Aug. 10, 2021. Adapted.

11. (FMP 2022) The general idea of the Text is the description of

1. human biologic stability
2. genetic mutation sources
3. species embryonic development
4. organic malfunction and disease
5. controlled computational analysis

12. (FMP 2022) In the 1ˢᵗ paragraph of the Text, in the fragment “Most of the time, this process unfolds with remarkable accuracy”, the highlighted word can be replaced, without any change in meaning, by

1. mistake
2. remedy
3. vagueness
4. exactitude
5. unreliability

13. (FMP 2022) In the 1ˢᵗ paragraph of the Text, in the fragment “but when it goes wrong, mutations can arise”, the highlighted word introduces the idea of

1. cause
2. addition
3. condition
4. opposition
5. consequence

14. (FMP 2022) In the 2ⁿᵈ paragraph of the Text, in the fragment “where and how heritable genetic mutations”, the highlighted word is associated with the idea that genetic mutations can be

1. lethal
2. acquired
3. inherited
4. infectious
5. contagious

15. (FMP 2022) In the 3ʳᵈ paragraph of the Text, in the fragment “has detected nine processes during which most human genetic mutations”, the highlighted word refers to

1. nine
2. study
3. mutation
4. processes
5. investigators

16. (FMP 2022) In the 4ᵗʰ paragraph of the Text, in the fragment “and represents one of the most comprehensive computational efforts”, the highlighted expression can be replaced, without any change in meaning, by

1. widest
2. narrowest
3. most exclusive
4. most controlled
5. most understanding

17. (FMP 2022) In the 6ᵗʰ paragraph of the Text, in the fragment “of computation and big data, we analyzed genomic variations”,the highlighted word refers only to

1. text readers and authors
2. Seplyarskiy and Women
3. Seplyarskiy and Soldatov
4. Sunyaev and Seplyarskiy
5. Sunyaev, Seplyarskiy and Soldatov

18. (FMP 2022) In the 7ᵗʰ paragraph of the Text, in the fragment “The analysis also detected a machinery involved in human gene regulation as a frequent malefactor in mutations”, the highlighted words are, respectively, synonymous to:

1. identified – villain
2. acknowledged – result
3. removed – consequence
4. eliminated – wrongdoer
5. disregarded – perpetrator

19. (FMP 2022) From the 8ᵗʰ paragraph of the Text, one can infer that the current aim of the research is to

1. develop new species.
2. control disease mutations.
3. change genome organization.
4. understand DNA duplication.
5. simulate cellular mechanisms.

20. (FMP 2022) In the 10ᵗʰ paragraph of the Text, in the fragment “The model may also serve to”, the highlighted verb form is related to the idea of

1. advise
2. obligation
3. prediction
4. permission
5. probability