Week 3: Inheritance and Genetics

Question 1

What is DNA? What is it made out of?

Answer 1

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

Question 2

What is a chromosome? How many pairs are there?

Answer 2

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)

Question 3

What is a gene?

Answer 3

Fundamental unit of DNA which includes regulatory and transcribed portions, and forms the base unit of heredity

Question 4

What is the function of a gene?

Answer 4

Genes encode for proteins produced by transcribing DNA into mRNA and translation in ribosomes then builds protein sequences from mRNA

Question 5

What is a mutation? What 3 types of mutations can introduce defects? Give the consequence of a gene mutation in two different cell types.

Answer 5

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

Question 6

What is a phenotype?

Answer 6

The composite of an organism’s observable characteristics or traits

Question 7

What is a karyotype?

Answer 7

The number and appearance of chromosomes in the nucleus of a eukaryotic cell

Question 8

What are alleles?

Answer 8

Alternative DNA sequences at the same physical gene locus; gives rise to different phenotypes

Question 9

What will happen if both alleles are the same? What happens if they are different?

Answer 9

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

Question 10

What are Mendel’s 3 laws of inheritance?

Answer 10

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

Question 11

What are 3 categories of genetic disorders? Give examples of at least 2 disease for each category.

Answer 11

Monogenic (Mendelian) disorders:
Neurofibromatosis
Adult polycystic kidney disease

Polygenic disorders:
Cardiovascular diseases
Diabetes
Stroke

Chromosomal aberrations:
Trisomy
Chronic myeloid leukemia
Turner’s syndrome

Question 12

What are single-gene disorders? Give 3 examples.

Answer 12

Mutations in a single gene (uncommon)

Cystic fibrosis
Sickle cell anemia
Huntington disease

Question 13

What are complex genetic disorders? Give 3 examples.

Answer 13

Effects of multiple genes in combination with lifestyle and environmental factors:

Cancer
Obesity
Diabetes

Question 14

Give 2 details about single gene and complex genetic disorders.

Answer 14

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

Question 15

What is gene therapy? Give 2 details about it. What are the 2 delivery systems available?

Answer 15

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

Question 16

Give 3 details about successful gene therapy for severe combined immunodeficiency.

Answer 16

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

Question 17

Explain Jessie Gelsinger’s story and why gene therapy can be unsuccessful.

Answer 17

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

Question 18

Explain the 3 problems associated with gene therapy.

Answer 18

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

Question 19

What are the 3 issues with pharmacogenomics?

Answer 19

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

Question 20

What are statistics regarding genetic diseases?

Answer 20

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)

Question 21

What was the timeline for the Human Genome Project?

Answer 21

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

Question 22

What are 3 findings of the HGP?

Answer 22

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)

Question 23

What are 7 benefits of the HGP?

Answer 23

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

Question 24

What is genetic testing?

Answer 24

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

Question 25

What are the 8 types of genetic testing?

Answer 25

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

Question 26

What are 5 ethical, legal, and social implications of genetic testing?

Answer 26

1. Access to and insurance coverage of genetic services and tests
2. Informed consent
3. Genetic discrimination
4. Privacy/disclosure of genetic information
5. Duty to inform

Question 27

What is a potential risk of genetic testing? What are 3 concerns consumers may have and what are the consequences of those concerns?

Answer 27

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

Question 28

Give details about the 8 types of genetic testing:

Diagnsotic
Predictive
Carrier
Prenatal
Preimplantation
Newborn screening
Single-gene disorder testing
Non-diagnostic testing

Answer 28

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)