Genetic Screening Flashcards

Question

What is thalassemia (a and B)?

Answer 1

• Both show autosomal recessive inheritance • Both can be detected by mean corpuscular hemoglobin and hemoglobin electrophoresis • Screening of young adults for the β-thalassemia carrier status has markedly reduced the birth incidence of β-thalassemia in Cyprus, Greece

Answer 2

Mutation in the CF transmembrane conductance regulator (CFTR) FYI- Incidence: 1 in 3,000 Caucasians or Ashkenazi Jewish, 1 in 8,000 Hispanics, 1 in 15,000 African Americans, 1 in 32,000 Asians. Detection • Immuno-reactive trypsinogen (IRT) in blood followed by a DNA test • DNA looking for ~32 of the most common mutations • Sweat chloride test (confirmatory test) Management • Antibiotics to combat respiratory infections, gene therapy, management of associated malabsorption

Answer 3

SCID is the result of genetic defects which impair the normal development of T-cells (x-linked recessive and autosomal recessive) SCID infants are phenotypically normal but acquire life-threatening infections within a few months of life Detection •Healthy T lymphocyte development will show presence of the by-product T cell receptor excision circles (TRECs) •TRECs are normally made in large numbers, while barely detectable in infants with SCID •TRECs are quantitated by real-time quantitative polymerase chain reaction (RT-qPCR) on DNA extracted from routine NBS cards Management • bone marrow transplant

Answer 4

* “My first patient is a 4-week-old girl coming in due to a positive newborn screen for cystic fibrosis (CF). Before coming to see me this afternoon, she will have a sweat test.” * She has no medical history for respiratory or gastrointestinal problems. Upon her arrival I learn that she has had a negative sweat test and may be a carrier of cystic fibrosis. * This is the first thing I explain to the parents, adding that being a carrier does not have any medical implications for their daughter. They look very relieved. * During the remainder of the session, we talk about how CF is inherited in an autosomal recessive fashion, and most likely that one of the parents is a CF carrier. * In addition, when their daughter is planning her family, she may have a similar consultation with genetics. * Finally, as it is possible that both parents could be carriers but only one passed on the mutant CF gene, I suggest that both parents be tested for carrier status. The parents opt to come back to have their carrier status tested and an appointment is made for next week.

Answer 5

* Most couples learn that they are carriers only after the birth of an affected child * Carrier screening offers the opportunity to identify couples at risk of having a child with a genetic disease • Screening for heterozygotes biochemical abnormalities – Specific molecular diagnostic tests (ASO array tests) or mutation analysis – Biochemical testing on tissue detects 50%, no need to know specific mutation

Answer 6

• Allelic heterogeneity • For cystic fibrosis, the DNA mutation panel can identify 25 of the most common mutations in the US population • A person who has been identified as a “non-carrier” – has the residual risk of being a carrier of an infrequent mutant allele, that is not included in the panel

Answer 7

• Options for a couple in which both partners are carriers – Choosing not to have biological children – Artificial insemination or egg donation – Prenatal diagnosis and termination of an affected pregnancy – Prenatal diagnosis and planning for the care of an affected child – No prenatal testing

Answer 8

• The most common issues involve: – Autonomy: client has the right to make own decisions • Complications include patient age or economic status • What to do when asked “what would you do?” Avoid answering! – Informed consent: knowledge of all possible consequences – The right to know or not know: Late onset diseases? – Coercion: is the client being persuaded by family or friends? – Confidentiality: no release of data to third parties including relatives • Insurance? – Reproductive decision making: DMD is tested but not Wilson’s?? • Sex selection??? – Testing of minors or mentally challenged persons: controversial, • Will the patient benefit from the test? • Is there a treatment or intervention?

Answer 9

The SHH gene encodes a protein that functions extracellularly to control a signaling pathway. Since SHH is expressed from specifically located cells, a concentration gradient of SHH protein is formed, with the highest concentration near the cells that secretes the protein. This concentration gradient is then interpreted via the pathway to direct tissue differentiation. • At the end of the SHH pathway, gene expression is indeed regulated via the two transcription factors (DNA binding proteins) CREBP and GLI

Answer 10

A receptor tyrosine kinase is not found in the SHH pathway; achondroplasia (a different disorder), is caused by a dominant gain of function variant in the FGFR3 gene. * Cholesterol is a lipid, SHH is a gene, SHH is a protein. To become activated, a portion of the SHH protein is first cleaved off, then what is left binds to cholesterol. For this reason, an enzyme deficiency disorder that leads to reduced cholesterol synthesis has a similar presentation as reduced SHH activity * SHH is extracellular, and it does not bind to actin.

Answer 11

The HOX genes and many other genes involved in regulation of gene expression contain the homeodomain which is a highly conserved set of amino acids that can bind to DNA

Answer 12

• The homeodomain can bind to the DNA • Then the bound protein can exert its regulatory effects on the DNA via transcriptional regulation • Some genes experience increased expression • Some genes might be repressed • The end result is appropriate cell determination and differentiation • Appropriate tissue structures are formed, and the fetus develops

Genetic Screening Flashcards

(36 cards)