The genetic basis of disease

Jackson, Maria; Marks, Leah; May, Gerhard; Wilson, Joanna B.

doi:10.1042/ebc20170053

Cited by 214 publications

(147 citation statements)

References 55 publications

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“…69XXX and low-level mosaicism), can be directly observed and screened via this protocol because of its unlimited resolution of structural variation. Although low-coverage PGT for aneuploidy is effective for detecting large (>10 Mbp) chromosomal aneuploidies, 1-2% of conceptions carry a de novo CNV or structural aneuploidy of >100 kb, a significant gap in the detection threshold 16 .…”

Section: Discussionmentioning

confidence: 99%

Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening

Murphy

Samarasekera

Macaskill

et al. 2020

Sci Rep

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Whole-genome sequencing of preimplantation human embryos to detect and screen for genetic diseases is a technically challenging extension to preconception screening. combining preconception genetic screening with preimplantation testing of human embryos facilitates the detection of de novo mutations and self-validates transmitted variant detection in both the reproductive couple and the embryo's samples. Here we describe a trio testing workflow that involves whole-genome sequencing of amplified DNA from biopsied embryo trophectoderm cells and genomic DNA from both parents. Variant prediction software and annotation databases were used to assess variants of unknown significance and previously not described de novo variants in five single-gene preimplantation genetic testing couples and eleven of their embryos. Pathogenic variation, tandem repeat, copy number and structural variations were examined against variant calls for compound heterozygosity and predicted disease status was ascertained. Multiple trio testing showed complete concordance with known variants ascertained by single-nucleotide polymorphism array and uncovered de novo and transmitted pathogenic variants. this pilot study describes a method of whole-genome sequencing and analysis for embryo selection in high-risk couples to prevent early life fatal genetic conditions that adversely affect the quality of life of the individual and families. Whole-genome sequencing in the iVf clinic. For over two decades, preimplantation genetic testing (PGT) has been available for couples who are aware they carry a genetic condition or have had a child affected by a genetic disease. In vitro fertilisation (IVF) used in conjunction with monogenic PGT is available for couples to prevent transmission of known hereditary monogenic disorders. PGT for aneuploidy screens embryos for large segmental or whole-chromosome copy number changes and is commonly used for older women (>35 years) who have a history of infertility, miscarriages or chromosomally abnormal conceptions 1-3. The most recent developments in clinical PGT are low-coverage next-generation sequencing and Karyomapping, which uses a highly polymorphic single-nucleotide polymorphism (SNP) microarray to identify disease-causing haplotypes. Nextgeneration sequencing PGT for aneuploidy (typically <0.1× depth) is useful for high-throughput screening at a reasonable cost for detecting chromosomal aneuploidies, structural variations and large copy-number variations (CNVs) 4-6. In addition to pedigree analysis for monogenic disorders, Karyomapping has been reported to identify partial chromosomal aneuploidies as small as 1.8 Mb 7. For couples seeking to ascertain their risk of having an affected child, around 6,000 diseases exist that may be genetically screened for 8. A mutation or disease-causing variant in one or both copies of approximately 5,000 human genes can cause a syndromic disease or phenotype 9-14. Between 0.5-5% of infants are born with a genetic condition or disorder 15,16. The preconception genetic screening...

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Section: Discussionmentioning

confidence: 99%

Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening

Murphy

Samarasekera

Macaskill

et al. 2020

Sci Rep

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“…As can be seen from the companion article of genetic basis for disease [2], the ability to use these techniques to test for inherited genetic disorders is important and indeed is forming a bigger and bigger role in our healthcare. The 100000 genomes project, launched by the U.K. prime minister in 2012 is a large genomic study and has demonstrated the utility of genomic medicine, enabling the diagnosis and further study of a range of genetic diseases and in the study and treatment of cancer [3].…”

Section: Genetic Testing and The Futurementioning

confidence: 99%

“…Indeed this may also move into the realm of preventative medicine, but here we have the ethical issue that containing a gene may only give a chance of disease and at what point do you decide to act. A further discussion of this can be found in the article of genetic disease [2]. There is also the ethical issue of both privacy and ownership of genetic information.…”

Section: Genetic Testing and The Futurementioning

confidence: 99%

Recombinant DNA technology and DNA sequencing

Roberts

2019

Essays in Biochemistry

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DNA present in all our cells acts as a template by which cells are built. The human genome project, reading the code of the DNA within our cells, completed in 2003, is undoubtedly one of the great achievements of modern bioscience. Our ability to achieve this and to further understand and manipulate DNA has been tightly linked to our understanding of the bacterial and viral world. Outside of the science, the ability to understand and manipulate this code has far-reaching implications for society. In this article, we explore some of the basic techniques that enable us to read, copy and manipulate DNA sequences alongside a brief consideration of some of the implications for society.

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“…Tumor/cancer is a chronic disease resulting from gradually accumulation of mutations or epigenetic alterations in our genetic material, DNA [1]. Ten to twenty percent cancer risk comes from hereditary factors and 80-90% of cancer risk from environmental factors [2].…”

Section: Introduction: Cancer and Cam-mediated Tumor Progression Andmentioning

confidence: 99%

METCAM/MUC18 Promotes Tumor Progression and Metastasis in Most Human Cancers

Wu¹

2020

Tumor Progression and Metastasis

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In addition to oncogenes and tumor suppressor genes, cell adhesion molecules (CAMs) also significantly contribute to tumor progression and metastasis. For the past two decades, we have demonstrated that METCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, orchestrates complex interactions of tumor cells with various stromal cells in the tumor microenvironment, resulting in augmentation or reduction of the metastatic potential of carcinoma cells. Here we show that METCAM/MUC18 plays a positive role in the tumor progression and metastasis in most human cancers, such as breast cancer, human melanoma and most mouse melanoma, nasopharyngeal carcinoma type III, prostate cancer LNCaP and DU145 cell lines, and perhaps angiosarcoma, gastric cancer, glioma, hepatocellular carcinoma, non-small cell lung adenocarcinoma, small cell lung cancer (SCLC), osteosarcoma, and human and mouse pancreatic cancer. Possible mechanisms in the METCAM/MUC18-mediated tumor progression and metastasis are proposed. Anti-METCAM/MUC18 antibodies and siRNAs may be used as therapeutic agents to treat these cancers.

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The genetic basis of disease

Cited by 214 publications

References 55 publications

Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening

Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening

Recombinant DNA technology and DNA sequencing

METCAM/MUC18 Promotes Tumor Progression and Metastasis in Most Human Cancers

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