Exam 11: Genetic Testing From Genes to Genomes, and the Ethics of Genetic Testing and Therapy

What are the main ethical arguments against genetic manipulation of the germ line?

Traditional prenatal diagnosis has typically meant analysing samples that have been recovered from the developing fetus by some type of invasive procedure. What is involved in these procedures?

Concerning prenatal diagnosis, which, if any, of the following statements is false? a) It relies on surgical procedures to recover fetal tissues from a pregnant woman. b) Chorion villus biopsies are typically taken around 16 weeks of gestation. c) Amniotic fluid samples allow culturing of fetal cells for cytogenetic analyses as well as allowing DNA analyses. d) There is always a small excess risk of miscarriage.

Mutation scanning and mutation testing can be used to identify pathogenic mutations. What is the essential difference between these two approaches?

In cancer testing biomarkers based on DNA variants or gene expression profiles are increasingly important. List four types of role that biomarkers can have in cancer testing and illustrate your answer with examples.

Multiplex ligation-dependent probe amplifaction (MLPA) is an important technology used in genetics research and genetic testing. What uses is it put to in a genetics service laboratory and what is the basis of the method.

Interpret the following DNA and amino acid variants: a) c.*15A>G b) p.Asp522del c) c.-22T>G d) c.121-6C>A

Concerning genetic screening, which, if any, of the following statements is false? a) Genetic screening is carried out primarily in communities and populations b) In carrier screening the motivation is to identify carriers of a mutant allele for a severe autosomal recessive disorder that has a high prevalence in the community or population. c) In most cases of pregnancy screening the motivation is to identify whether a fetus carries a genetic variant associated with a harmful single gene disorder. d) In newborn screening the motivation is often to target early treatment for serious disorders for which early intervention can make a significant difference.

Fill in the blanks below with single words. ______1______ genetic diagnosis is carried out in the contact of assisted reproduction. It can be technically challenging because quite often analysis is carried out on a ____2_____ cell, that may be from the early stage _____3____ (the stage at which the embryo consists of just a very few cells that are individually called ____4_____ ). Another alternative, that can be used when the mother is at risk of transmitting a harmful genetic variant, is to infer the genotype of the _____5_____ by analysing a ____6____ ____7_____ (a cell that is created by one of the asymmetric cell divisions in female ____8_____). Because of technical difficulties in analysing a _____2_____ cell, some centers prefer to analyse _____9_____ cells from a late-stage _____3____.

Two important ethical principles that relate to genetic testing in children are the principle of beneficence and the "right to an open future". Explain what is meant by these principles.

Fill in the blanks below with single words. Traditional ______1______ diagnosis has involved _____2______ surgical procedures in which a sample of fetal cells is recovered and analysed. There have been two major approaches. In one case a sample is taken from the _____3____ (the outermost extra-embryonic ____4_____ ). Typically this sample is taken in the ____5______ trimester of pregnancy. In the other case, a sample of _____6_____ fluid is taken that will contain cells from the _____7______ , an inner extra-embryonic ____4_____. This procedure, called ____8_____ is taken at, or close to, 16 weeks of gestation; it provides fetal cells that can be processed to allow ____9_____ analyses as well as DNA analyses. Because of the surgical procedures involved there is a small excess risk of ____10_____. As a result, there has been a trend to develop non-_____2______ ______1______ diagnosis. That has been fuelled by _____11_______ ______12______ sequencing of DNA from maternal ____13____.

Interpret the following DNA and amino acid variants: a) g.410_411insC b) p.Gly418* c) c.*62A>T d) c.142+4C>T