Descodificando o Genoma Humano
DOI:
https://doi.org/10.25753/BirthGrowthMJ.v32.i3.27586Palavras-chave:
amplificação de sonda dependente de ligação multiplex, cariótipo, hibridização genómica comparativa, hibridização in situ fluorescente, reação de polimerização em cadeia, sequenciação de nova geração, sequenciação de SangerResumo
O neonatologista é frequentemente o primeiro clínico a confrontar-se com condições genéticas não diagnosticadas no período pré-natal. Os avanços tecnológicos no campo da genética nas últimas décadas trouxeram possibilidades nunca antes imaginadas. Distantes estão os tempos em que pouco mais poderia ser oferecido aos doentes do que um cariótipo de sangue periférico. Metodologias mais recentes, como hibridização genómica comparativa ou sequenciação de Sanger e sequenciação de nova geração, permitem analisar mais detalhadamente o genoma humano, quer ao nível dos grandes rearranjos (deleções, duplicações), quer de variantes pontuais potencialmente patogénicas. Estas tecnologias de ponta têm sido úteis na descoberta de genes implicados em doenças há muito entendidas como de origem genética, mas cuja etiologia permanecia desconhecida. Apesar dos bons presságios, nenhum método é autossuficiente e todos apresentam as suas limitações. O objetivo desta revisão é atualizar os clínicos sobre os testes genéticos atualmente disponíveis e utilizados. Recordando que o primeiro genoma humano foi sequenciado há pouco mais de vinte anos, que novidades trarão os próximos vinte?
Downloads
Referências
Nakamura Y. DNA variations in human and medical genetics: 25 years of my experience. J Hum Genet. 2009;54(1):1-8.
Levy B, Burnside RD. Are all chromosome microarrays the same? What clinicians need to know. Prenat Diagn. 2019;39(3):157-64.
Stuppia L, Antonucci I, Palka G, Gatta V. Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases. Int J Mol Sci. 2012;13(3):3245-76.
Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22(2):245-57.
Jorde LB. Medical genetics. 5th edition ed. Philadelphia, PA: Elsevier; 2016.
Zarrei M, MacDonald JR, Merico D, Scherer SW. A copy number variation map of the human genome. Nature Reviews Genetics. 2015;16(3):172-83.
Campbell M. Missense, Nonsense and Frameshift Mutations: A Genetic Guide2020 01/05/2022. Available from: https://www.technologynetworks.com/genomics/articles/missense-nonsense-and-frameshift-mutations-a-genetic-guide-329274.
Silva M, de Leeuw N, Mann K, Schuring-Blom H, Morgan S, Giardino D, et al. European guidelines for constitutional cytogenomic analysis. Eur J Hum Genet. 2019;27(1):1-16.
Wallace SE, Bean LJ. Educational Materials — Genetic Testing: Current Approaches. 2017 Mar 14 [Updated 2020 Jun 18] 1993-2022. In: GeneReviews® [Internet] [Internet]. Seattle (WA): University of Washington, Seattle. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279899/.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24.
Harrison SM, Biesecker LG, Rehm HL. Overview of Specifications to the ACMG/AMP Variant Interpretation Guidelines. Curr Protoc Hum Genet. 2019;103(1):e93.
Clarke A, Murray A, Sampson J. Harper’s Practical Genetic Counselling. 8th Edition ed. London: CRC Press; 2019.
Ulrich AB, Pour PM. Cell Lines. In: Brenner S, Miller JH, editors. Encyclopedia of Genetics. New York: Academic Press; 2001. p. 310-1.
O’Connor C. Karyotyping for chromosomal abnormalities2008; 1(1):27. Available from: https://www.nature.com/scitable/topicpage/karyotyping-for-chromosomal-abnormalities-298/.
LaFramboise T. Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic Acids Res. 2009;37(13):4181-93.
NCBI. Polymerase Chain Reaction (PCR)2017. Available from: https://www.ncbi.nlm.nih.gov/probe/docs/techpcr/.
Joshi M, Deshpande J. Polymerase chain reaction: methods, principles and application. International Journal of Biomedical Research. 2010;2(1):81-97.
Jalali M, Zaborowska J, Jalali M. Chapter 1 - The Polymerase Chain Reaction: PCR, qPCR, and RT-PCR. In: Jalali M, Saldanha FYL, Jalali M, editors. Basic Science Methods for Clinical Researchers. Boston: Academic Press; 2017. p. 1-18.
Caetano-Anollés D. Polymerase Chain Reaction. In: Maloy S, Hughes K, editors. Brenner’s Encyclopedia of Genetics (Second Edition). San Diego: Academic Press; 2013. p. 392-5.
Rajan-Babu I-S, Chong SS. Triplet-repeat primed PCR and capillary electrophoresis for characterizing the fragile X mental retardation 1 CGG repeat hyperexpansions. Clinical Applications of Capillary Electrophoresis: Springer; 2019. p. 199-210.
Jama M, Millson A, Miller CE, Lyon E. Triplet Repeat Primed PCR Simplifies Testing for Huntington Disease. The Journal of Molecular Diagnostics. 2013;15(2):255-62.
Filipovic-Sadic S, Sah S, Chen L, Krosting J, Sekinger E, Zhang W, et al. A Novel FMR1 PCR Method for the Routine Detection of Low Abundance Expanded Alleles and Full Mutations in Fragile X Syndrome. Clin Chem. 2010;56(3):399-408.
Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30(12):e57.
Moelans CB, Atanesyan L, Savola SP, van Diest PJ. Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA). Methods Mol Biol. 2018;1708:537-49.
Slatko BE, Gardner AF, Ausubel FM. Overview of Next-Generation Sequencing Technologies. Curr Protoc Mol Biol. 2018;122(1):e59.
Fridovich-Keil JL. Human Genome Project2022 01/05/2022]. Available from: https://www.britannica.com/event/Human-Genome-Project.
Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26(10):1135-45.
van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C. Ten years of next-generation sequencing technology. Trends Genet. 2014;30(9):418-26.
Liu S, Thaler DS, Libchaber A. Signal and noise in bridging PCR. BMC Biotechnol. 2002;2:13.
Leggett RM, Clark MD. A world of opportunities with nanopore sequencing. Journal of Experimental Botany. 2017;68(20):5419-29.
Rhoads A, Au KF. PacBio Sequencing and Its Applications. Genomics Proteomics Bioinformatics. 2015;13(5):278-89.
Monaghan KG, Leach NT, Pekarek D, Prasad P, Rose NC. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(4):675-80.
Fernandez-Marmiesse A, Gouveia S, Couce ML. NGS technologies as a turning point in rare disease research, diagnosis and treatment. Curr Med Chem. 2018;25(3):404-32.
Rehm HL. Disease-targeted sequencing: a cornerstone in the clinic. Nature Reviews Genetics. 2013;14(4):295-300.
Miller DT, Lee K, Chung WK, Gordon AS, Herman GE, Klein TE, et al. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1381-90.
República Ad. Diário da República n.º 18/2005, Série I-A de 2005-01-26, páginas 606 - 611. 2005-01-26.
Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013;131(3):620-2.
Counselors NSoG. Genetic Testing of Minors for Adult-Onset Conditions2018 29/03/2022. Available from: https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for-adult-onset-conditions.
Grady C. Ethics and genetic testing. Adv Intern Med. 1999;44:389-411.
ASHG. The Genetic Information Nondiscrimination Act (GINA)22/05/2022. Available from: https://www.ashg.org/advocacy/gina/.
Downloads
Publicado
Como Citar
Edição
Secção
Licença
Direitos de Autor (c) 2023 Diogo Fernandes da Rocha, Gustavo Rocha, Pedro Louro
Este trabalho encontra-se publicado com a Creative Commons Atribuição-NãoComercial 4.0.
Copyright and access
This journal offers immediate free access to its content, following the principle that providing free scientific knowledge to the public provides greater global democratization of knowledge.
The works are licensed under a Creative Commons Attribution Non-commercial 4.0 International license.
Nascer e Crescer – Birth and Growth Medical Journal do not charge any submission or processing fee to the articles submitted.
