Genetic Alterations Flashcards
(58 cards)
1
Q
X-linked dominant
A
- Described a dominant trait or disorder caused by a mutation in a gene on the X chromosome
- Both males and females express the phenotype, although, although males affected tend to have a more severe phenotype
- Only one affected X chromosome is required to cause the disease
2
Q
Examples of X-linked dominant disease
A
- Fragile X syndrome
3
Q
What is the probability pf transmitting an X-linked dominant gene mutation through the mother (female)?
A
- 50% probability for each child regardless of gender
- 50% affected and 50% unaffected
4
Q
What is the probability pf transmitting an X-linked dominant gene mutation through the father (male)?
A
- 50% are affected (ALL FEMALES)
- 50% are unaffected (ALL MALES)
5
Q
X-linked dominant gene mutation from an affected male to his offspring VS
X-linked dominant gene mutation from an affected female to her offspring
A
- Affected male to his offspring: All of his daughters and none of his sons will inherit the mutation
- Affected female to her offspring: Each child, regardless of gender, has a 50% chance of inheriting this mutation
6
Q
X-linked recessive
A
- A mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males who are hemizygous for the gene mutation (i.e., they only have one X chromosome) and in females who are homozygous for the gene mutation (i.e., they have a copy of the gene mutation on each of their two X chromosomes)
- Males only require one mutated X chromosome (since they only have one X chromosome, to begin with) in order to cause the disease
- Phenotype expressed in males only
- Affected males are always related to each other through females. MALE –> TO MALE TRANSMISSION DOES NOT OCCUR
- Females are less likely to have an x-linked recessive disorder because they have two X chromosomes
- If females do inherit it, it will most likely be less severe
7
Q
Examples of X-linked recessive disorders
A
- Hemophilia
- Fabry disease
8
Q
Autosomal Dominant
A
- Describes a trait/disorder in which the phenotype is expressed in those who have inherited only one copy of a particular gene mutation (heterozygotes)
- Specifically refers to a gene on one of the 22 pairs of autosomes (non-sex chromosomes)
- Only one copy of the abnormal gene
- Not sex linked
9
Q
What is the chance of passing on an autosomal dominant disorder from parent to offspring?
A
- Each offspring has a 50% chance of inheriting it
- Son and daughters of an affected parent are equally likely to inherit and transmit the disorder
10
Q
Examples of autosomal dominant disorders
A
- Huntington disease
- Marfan syndrome
11
Q
Autosomal Recessive
A
- Describes a trait/disorder requiring the presence of two copies of a gene mutation at a particular locus in order to express the observable phenotype
- Refers to genes on one of the 22 pairs of autosomes (non-sex chromosomes)
-
Needs two copies of the mutation for an offspring to exhibit the phenotype
- Generally seen in a single generation of a family
- Each offspring has a 25% chance of inheriting it
12
Q
Examples of autosomal recessive disorders
A
- Cystic fibrosis
- Sickle cell disease
13
Q
What is the probability of transmitting an autosomal recessive gene mutation to an offspring if one parent carries the mutation?
A
- 50% are carriers
- 50% are non-carriers
- NO ONE SHOWS!
14
Q
What is the probability of transmitting an autosomal recessive gene mutation to an offspring if both parents carry the mutation?
A
- 25% are noncarriers and 50% are carriers } (unaffected)
- 25% are homozygotes for the mutation (affected)
15
Q
What is the probability of transmitting an autosomal recessive gene mutation to an offspring if one parent is affected and one parent is a carrier of the mutation?
A
- 50% are carriers (unaffected)
- 50% are homozygotes for the mutation (affected)
16
Q
Identify 7 disorders/diseases with a strong familial history
A
- CAD
- Stroke
- HTN
- Cancer
- Diabetes
- Pulmonary conditions
- Mental Illness
17
Q
What increases an individual’s genetic susceptibility to developing CAD?
A
- Two or more closed relatives with CAD
- Female relatives with CAD
- Presence of related disorders such as diabetes in a close relative
- Presence of multiple established/emerging risk factors in close family members
- Early-onset of CAD ( <55 for men, <65 for women)
18
Q
What two common genetic variants or single-nucleotide polymorphisms (SNPs) were consistently associated with total stroke (all types) and ischemic stroke in white individuals?
A
- Located on chromosome 12p13 near the gene NINj2, which encode ninjurin 2
19
Q
What is GINA and how is it related to genetic discrimination?
A
- Stands for Genetic Information Non-Discrimination Act
- A federal law passed in 2008
- Prohibits discrimination in employment and health insurance coverage based on genetics
- Prohibits insurance companies from requesting/requiring genetic information of an individual or their family, or using genetic information for decisions regarding coverage, rates, or preexisting conditions
20
Q
What is one thing GINA does not do?
A
- It does not extend to:
- Life insurance
- Disability insurance
- Long0term care insurance
21
Q
What does a patient need to be aware of before they order a genetic test?
A
- Patients need to be aware that they need to have purchased forms of insurance (life, disability, long-term care) prior to genetic testing
22
Q
Mutations in BRCA 1 and BRCA 2 genes are associated with what?
A
- Hereditary breast and ovarian cancer
23
Q
When BRCA 1 and BRCA 2 genes are functioning normally, what do they act as?
A
- They both act as tumor suppressor genes
24
Q
On what chromosomes do BRCA 1 and BRCA 2 mutations occur?
A
- BRCA 1 occurs on chromosome 17
- BRCA 2 occurs on chromosome 13
25
How are the mutations for HFE inherited?
* They are inherited in an autosomal recessive manner
26
What is HFE associated hereditary hemochromatosis (HFE-HH) and what are the signs and symptoms?
* A condition in which there is high absorption of iron from the intestinal mucosa
* **Signs/Symptoms:**
* Excessive storage of iron in the liver, skin, pancreas, heart, joints, and testes
* Abdominal pain
* Weakness
* Lethargy
* Weight loss
27
What are the two most common mutations associated with HFE-HH and on which chromosome are they located?
* p. Cys282T yr and p.His63Asp yr
* An individual can be **homozygous** for the p. Cys282 T yr mutation **_(greater risk for iron overload)_****_OR_**
* A **compound heterozygote** for both mutations ( p. Cys282T yr and p.His63Asp yr)
* They are located on **chromosome 6**
28
At what age do symptoms usually occur for HFE-HH?
* Between the ages of 40 to 60 years
29
What is a major complication of HFE and what can worsen it?
* Liver cirrhosis --\> Individuals **_treated prior to the onset of cirrhosis_** have a normal life span
* Alcohol consumption can worsen symptoms
30
What is the recommended treatment for HFE-HH?
* Weekly periodic phlebotomy until serum ferritin levels are 50ng/ml or lower
31
Is there genetic testing available for "normal" ( age of onset \>60 years and not associated with an extensive family hx of AD) AD?
* There is **no** current genetic testing available for "normal" AD
* The association of the **_APOE e4 allele with AD is insignificant_**
32
What is familial AD (FAD)?
* FAD characterizes families that have **more than one member with AD** and usually **implies multiple affected persons in more than one generation**
33
What does early-onset FAD (EOFAD) refer to?
* EOFAD refers to families in which the onset is consistently before the age of 60 to 65 years and often before the age of 55 years
34
What percentage of early-onset AD is familial and what percentage is inherited in an autosomal dominant manner?
* Approximately 60% of early-onset AD is familial
* Approximately 13% is inherited in an autosomal dominant manner
35
What are the three types of early-onset AD?
1. AD1
2. AD3
3. AD4
36
AD1 is caused by mutations on what gene located on what chromosome?
* Caused by mutations in APP located on chromosome 21
37
AD3 is caused by mutations on what gene located on what chromosome?
* Caused by mutations in PSEN1 gene located on chromosome 14
38
AD4 is caused by mutations on what gene located on what chromosome?
* Caused by mutations in PSEN2 located on chromosome 1
39
What type of genetic testing is available for the three types of early-onset AD?
* Molecular genetic testing is available for the three types of early-onset AD (AD1, AD3, AD4)
* There is **NO** treatment however
40
What is genomics?
* The study not just of single genes but of the functions and interactions of many genes in the genome.
41
How does the study of genomics affect healthcare?
* Understanding how variations in an individual’s DNA may affect disease and health is the focus of genomic medicine. This knowledge can lead to:
* Innovative ways to diagnose disease
* Earlier detection, by identifying genetic predisposition to a particular disease
* New approaches to treatment
* Development of designer drugs that target a mutation or its products (pharmacogenomics)
42
What is penetrance?
* The proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder
* Most often **refers to autosomal dominant conditions**
* **A greater penetrance means that it is more likely an offspring will have it**
43
How do you calculate penetrance?
## Footnote
Number of individuals with clinical features **(Nclinical)**
**——————————————————————————**X 100 = **Penetrance**
Number of individuals with a disease-causing mutation **(Nmutation)**
44
What does complete penetrance refer to?
* Refers to clinical symptoms being present in **_all_** individuals who have the disease-causing mutation
45
What does incomplete penetrance refer to?
* Refers to clinical symptoms **not** being present in all individuals who have the disease-causing mutation
46
What does consanguinity refer to?
* Refers to genetic relatedness between individuals descended from at least one common ancestor --\> Incest
* Can _decrease_ genetic variability
* _Increases_ risk for mutations
47
What does anticipation refer to?
* Refers to the tendency in certain genetic disorders for individuals in successive generations to present at an earlier age and/or with more severe manifestations
48
Anticipation is often observed in disorders resulting from what?
* Often is observed in disorders resulting from the expression of a **_trinucleotide repeat mutation_** that tends to increase in size and have a more significant effect when passed from one generation to the next
* Example: Huntington Disease
49
Genotype VS phenotype?
* **Genotype:** Refers to the genetic makeup/composition
* **Phenotype:** The observable physical/biochemical characteristics of the expression of a gene; the clinical presentation of an individual with a particular genotype
50
What are predictive and pre-symptomatic genetic tests?
* Used to find gene changes that increase a person's likelihood of developing diseases in **asymptomatic** individuals with a **_family history of a genetic disorder_** and a potential risk of eventually developing the disorder
51
What are the two types of predictive testing?
1. Presymptomatic testing
2. Predispositional testing
52
What is presymptomatic testing?
* Refers to testing of an asymptomatic individual in whom the discovery of a gene mutation indicates certain development of findings related to a specific diagnosis at some future point
* A negative result excludes the diagnosis --\> Means **NO** mutation was found
* Mutation found --\> Means individual will develop disorder at a future point
53
What is predispositional testing?
* Refers to testing an asymptomatic individual in whom the discovery of a gene mutation indicates the eventual development of findings related to a specific diagnosis is likely, but not certain
* Mutation confers susceptibility
* Mutation found --\> Higher risk of developing disorder but not 100%
* Mutation NOT found --\> Lower risk of developing disorder but not 0%
54
What does carrier testing used for?
* Used to find people who "carry" a change in a gene that is linked to a disease
* Usually offered to people who have a family history of a specific inherited disease or who belong to certain ethnic groups that have a higher risk of specific inherited diseases
55
What type of gene mutations is carrier testing used for?
* Used for autosomal recessive gene mutations
56
What is pharmacogenomic testing used for?
* Provides information about how certain medications are processed by an individual's body
* Helps providers choose medicines that work best for an individual's genetic makeup
57
What is diagnostic testing?
* Testing used to confirm or exclude a known or suspected genetic disorder in a symptomatic individual or, prenatally, in a fetus at risk for a certain genetic condition
58
Define epigenetics
* Processes that modulate how a given set of genomic information gives rise to a phenotype
* Refers to the area outside of the gene area
* Environment has an impact on this
