Week 3: Inheritance and Genetics Flashcards
What is DNA? What is it made out of?
Nucleic acid is a molecule that carries most of the genetic instructions used in development, functioning, and reproduction of all known living organisms and many viruses
Made of 4 bases: adenine, guanine, cytosine, and thymine
What is a chromosome? How many pairs are there?
A packaged and organized structure containing most of the DNA of a living organism
23 pairs (22 pairs of autosomes and 1 pair of allosome)
What is a gene?
Fundamental unit of DNA which includes regulatory and transcribed portions, and forms the base unit of heredity
What is the function of a gene?
Genes encode for proteins produced by transcribing DNA into mRNA and translation in ribosomes then builds protein sequences from mRNA
What is a mutation? What 3 types of mutations can introduce defects? Give the consequence of a gene mutation in two different cell types.
A permanent change of the nucleotide sequence of the genome of an organism
Radiation, chemical exposure, and simple copying errors introduce defects
In somatic cells these can cause disease; in oncogenes, cancer can result
What is a phenotype?
The composite of an organism’s observable characteristics or traits
What is a karyotype?
The number and appearance of chromosomes in the nucleus of a eukaryotic cell
What are alleles?
Alternative DNA sequences at the same physical gene locus; gives rise to different phenotypes
What will happen if both alleles are the same? What happens if they are different?
If both alleles are the same, they and the organism are homozygous (DD or dd) with respect to that gene
If the alleles are different, they and the organism are heterozygous (Dd) with respect to that gene
What are Mendel’s 3 laws of inheritance?
Law of segregation: during gamete formation, the alleles for each gene segregate from each other so that each gamete carries only one allele for each gene
Law of independent assortment: genes for different traits can segregate independently during the formation of gametes
Law of dominance: some alleles are dominant while others are recessive; an organism with at least one dominant allele will display the effect of the dominant allele
What are 3 categories of genetic disorders? Give examples of at least 2 disease for each category.
Monogenic (Mendelian) disorders:
Neurofibromatosis
Adult polycystic kidney disease
Polygenic disorders:
Cardiovascular diseases
Diabetes
Stroke
Chromosomal aberrations:
Trisomy
Chronic myeloid leukemia
Turner’s syndrome
What are single-gene disorders? Give 3 examples.
Mutations in a single gene (uncommon)
Cystic fibrosis
Sickle cell anemia
Huntington disease
What are complex genetic disorders? Give 3 examples.
Effects of multiple genes in combination with lifestyle and environmental factors:
Cancer
Obesity
Diabetes
Give 2 details about single gene and complex genetic disorders.
No clear-cut pattern of inheritance; difficult to determine a person’s risk of inheriting these disorders
Complex disorders are difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified
What is gene therapy? Give 2 details about it. What are the 2 delivery systems available?
Introduction of normal genes into cells that contain defective genes to reconstitute a missing protein product
Used to correct a deficient phenotype so that sufficient amounts of a normal gene product are synthesized to improve a genetic disorder
Modification of cells by transferring desired gene sequences into the genome
In vivo: delivery of genes take place in the body
Ex vivo: delivery takes place out of the body and then cells are placed back into the body
Give 3 details about successful gene therapy for severe combined immunodeficiency.
Infants with combined immunodeficiency are unable to mount an adaptive immune response, because they have a profound deficiency of lymphocytes due to a deficiency of adenosine deaminase
In these patients; peripheral T cells were transduced with a vector bearing the gene for adenosine deaminase
The experiment was extremely labor intensive, because mature peripheral-blood T cells were modified rather than stem cells, and the procedure therefore had to be repeated many times to achieve success
Explain Jessie Gelsinger’s story and why gene therapy can be unsuccessful.
Jessie Gelsinger: a gene therapy patient who lacked ornithine transcarbamylase activity died in 1999 due to multi-organ failure following gene therapy
One problem with gene therapy is that one does not have control over where the gene will be inserted into the genome
The location of a gene in the genome is of importance for the degree of expression of the gene and for the regulation of the gene (the so-called “position effect”), and thus the gene regulatory aspects are always uncertain after gene therapy
Explain the 3 problems associated with gene therapy.
Short lived:
Hard to rapidly integrate therapeutic DNA into genome and rapidly dividing nature of cells prevent gene therapy from long time
Would have to have multiple rounds of therapy
Viral vectors and immune response:
Patient could have toxic, immune, inflammatory response; also may cause once inside
Multigene disorders:
Heart disease, high blood pressure, Alzheimer’s, arthritis, and diabetes are hard to treat because you need to introduce more than one gene
What are the 3 issues with pharmacogenomics?
Drugs can be dangerous:
Many people have serve adverse reactions to drugs
Many people respond to drugs at different doses
Many drug treatments are horrible unpleasant, painful
Drugs are expensive (to take and make):
Ineffective drugs are a waste of money to take
Drug development needs to account for response variability
Genetics provide a priori information:
Genetics don’t change (except in cancer)
Genetics can point to the cause not just the symptom
What are statistics regarding genetic diseases?
Each year more than 3 million children born with a serious genetic defect die; most of these deaths (90%) occur in developing countries
U.S.: 1% chance of having an inherited disease at birth
Approximately 5% of the world’s population carries trait for hemoglobin disorders (mainly sickle cell and thalassemia)
What was the timeline for the Human Genome Project?
1990: Project initiated as joint effort of the U.S. Department of Energy and the NIH
June 2000: completion of a working draft of the entire human genome
February 2001: analyses of the working draft are published
April 2003: HGP sequencing is completed and Project is declared finished 2 years ahead of schedule
What are 3 findings of the HGP?
Human genome contains 3 billion chemical nucleotide bases (A, C, T, and G)
Average gene consists of 3000 bases, but sizes vary greatly, with the largest known human gene being dystrophin at 2.4 million bases
Total number of genes: estimated at around 30,000 (much lower than previous estimates of 80,000 to 140,000)
What are 7 benefits of the HGP?
Improved diagnosis of disease
Detected genetic predispositions to disease:
Screening advice
Risk factor modification
Create drugs based on molecular information
Design “custom drugs” (pharmacogenomics) based on individual genetic profiles
Use gene therapy for treatment
Identify potential suspects whose DNA may match evidence left at crime scenes
Exonerate people wrongly accused of crimes
What is genetic testing?
Analysis of chromosomes (DNA), proteins, and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes for clinical purposes
A genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder
What are the 8 types of genetic testing?
Diagnostic testing
Predictive testing
Carrier testing
Prenatal testing
Preimplantation
Newborn screening
Testing for diseases caused by a single gene disorder
Non-diagnostic testing to identify an individual
What are 5 ethical, legal, and social implications of genetic testing?
- Access to and insurance coverage of genetic services and tests
- Informed consent
- Genetic discrimination
- Privacy/disclosure of genetic information
- Duty to inform
What is a potential risk of genetic testing? What are 3 concerns consumers may have and what are the consequences of those concerns?
Concerns about inappropriate uses of genetic information may impede the application of genetic discoveries
Consumers may be:
Unwilling to use genetic services:
Weaken consumer demand and subsequently inhibit the development of new genetic services and technologies
Less likely to participate in genetic research:
Needs adequate numbers of participants to evaluate and assess promising services and technologies
Reluctant to share family history from genetic tests:
Which may diminish health professionals’ ability to help patients
Give details about the 8 types of genetic testing:
Diagnsotic
Predictive
Carrier
Prenatal
Preimplantation
Newborn screening
Single-gene disorder testing
Non-diagnostic testing
Diagnostic testing: confirm or rule out a disorder
Predictive testing: aimed at presymptomatic or predisposition; offered to asymptomatic individual with a family history of genetic disorder; indicated if early diagnosis helps for preventative treatment
Carrier testing: useful to prevent transmission
Prenatal testing: amniocentesis and blood or biopsy test; issues with regard to treatment or termination of pregnancy
Preimplantation: alternative to prenatal; limited in conditions which may be tested and cost is high
Newborn screening: most screenings are mandated by the states
Testing for diseases caused by a single gene disorder
Non-diagnostic testing to identify an individual (legal purposes)
