1
Q
On a pedigree drawing how are males and females represented?
A
- Males are represented by squares
- Females represented by circles
2
Q
On a pedigree diagram how are partners represented?
A
- Partners represented by a line between the two of them
3
Q
On a pedigree diagram how are siblings represented?
A
- Siblings are represented by a line above them
4
Q
On a pedigree diagram how are carriers and the affected represented?
A
- Affected people are completely shaded
- Carriers can either be unshaded or have a dot in them
5
Q
On a pedgree diagram how are children represented?
A
- Children are represented by a line running down from the parents
6
Q
What does this symbol represent on a pedigree diagram
A
- Represents a consanguineous partenership (Partners are related to each other)
7
Q
What does this symbol represent on a pedigree diagram?
A
- Indicates that the person is deceased
8
Q
What do these 2 symbols represent on a pedigree diagram?
A
- Triangle represents spontaneous abortion
- Triangle with the line through it represents therapeutic abortion
9
Q
What do these 2 symbols represent on a pedigree diagram?
A
- Angular lines, with horizontal line connecting them, running down to siblings of same sex indicates monozygotic twins (identical twins)
- Angular lines, without horizontal line connecting them, which run down to siblings of different sex indicates dizygotic twins (Non-identical twins)
10
Q
What does this symbol represent on a pedigree diagram?
A
- Represents pregnancy
11
Q
What is autosomal dominant inheritance?
A
- A form of inheritance in which an individual only needs to have one copy of the mutant allele in order to be affected (herteozygous for the mutant allele).
12
Q
For autosomal dominant inheritance why don’t you usually see people with a homozygous genotype?
A
- Because usually if a person has both copies of the mutant allele (homozygous for the mutant allele) is in-utero lethal which means the embryo won’t survive the pregnancy
13
Q
What are some of the features of a pedigree diagram showing autosomal dominant inheritance
A
- Multiple generations affected
- Both sexes affected equally
- Male to female & female to male transmission
14
Q
In autosomal dominant inheritance what is the risk of offspring being affeceted?
A
50%
15
Q
Most people who are affected by an autosomal dominant disorder will have a parent that is affceted. What are the two exceptions to this rule?
A
- De novo mutations - New mutation within a persons genome may mean that that person develops an autosomal dominant disorder without either parent being affected
- Incomplete penetrance - Results in offspring not showing any symptoms of the disorder (not showing the phenotypes) despite having inherited the mutant from their parents (they have the genotype).
16
Q
Define the term “penetrance”
A
The percentage/proportion of individuals who carry the mutation and develop symptoms of the disorder
17
Q
What is age-dependent penetrance?
A
When the penetrance for a particular disorder increases as individuals get older.
18
Q
What type of penetrance do most autosomal dominant disorder show?
A
Reduced penetrance
19
Q
What is reduced penetrance?
A
When individuals who must possess the mutant allele for a particular disorder show absolutely no manifestations/symptoms of that disorder.
20
Q
Apart from reduced penetrance what are some of the other characteristics of autosomal dominant inheritance?
A
- Variable expressivity - Idea that the severity of symptoms/symptoms themselves can vary between individuals with the same mutation
- New mutation rate - New muation rate (de novo mutation rate) varies between different autosomal dominant disorders
- Somatic mosaicism
- Germ-line mosaicism
- Anticipation - Worsening of disease severity in successive generations
21
Q
Explain the idea of Somatic mosaicism
A
- Refers to the presence of 2 or more populations of cells with different genotypes within the somatic cells of an individual due to the prescence or absence of a new mutation.
- The new mutation developes at an early stage of embryogenesis.
- Mutation only affects some of the somatic cells so some tissues/cells will reamin unaffected
22
Q
Explain the idea of germline mosaicism (Gonadal mosaicism)
A
- Refers to the presence of 2 or more populations of cells with different genotypes within the gametes of an individual due to a new mutation
- New mutation develops during oogenesis or spermatogenesis
- Mutation can be passed down to offspring depending on whether the gametes responsible for fertilisation have the mutation or not
23
Q
What is autosomal recessive inheritance?
A
- A form of inheritance in which an individual needs to have both copies of a mutated allele in order to be affected
- Person can either be homozygous for the mutant allele or be a compound heterozygote
24
Q
What is meant by the term compound heterozygote and how does it compare to being a homozygote
A
- A person is a compound heterozygote when they have 2 mutations within the same gene but these 2 mutations are different so they have 2 different recessive alleles
- A person is a homozygote when they have 2 mutations within the same gene but these 2 mutations are exactly the same so they have 2 of the same recessive allele
25
What are some of the features of a pedigree diagram showing autosomal recessive inheritance?
* Carriers (heterozygote) not affected
* Both sexes affected
* Male to female and female to male transmission
* Usually one generation affected
26
What are some features of autosomal recessive inheritance?
* Trait often found in clusters of siblings but not in parents & offspring.
* Biological parents of an affected child are usually both heterozygous
* Recurrence risk = 1/4 for each sibling of affected person.
* Carrier probability =2/3 for unaffected siblings of affected person.
* All offspring of affected person are obligate carriers.
27
What is meant by the term obligate carrier?
Somebody who may be unaffected but must carry a copy of the abnormal gene based on analysis of family history.
28
In autosomal recessive inheritance how can a child still be affected if only one of their biological parents are heterozygous for the mutant allele?
* A new mutation occurs on the gamete inherited from the other parent
* Uniparental isodisomy occurs resulting in the offspring inheriting two copies of the heterozygous parent’s mutated allele
29
What is x-linked inheritance?
* A form of inheritance in which a mutation within a gene on the X-chromosome (X-linked gene) leads to a male developing a disorder
30
Why can females be homozygous/heterozygous for X-linked genes while males can only be Hemizygous?
* Females can be either homozygous or heterozygous because they have two X chromosomes and therefore have two copies of X-linked genes
* Males can only be hemizygous because they have one X and a Y chromosome and so only have a single copy of X-linked genes
31
X-linked inheritance can be dominant or recessive. What are some features of both types of X-linked inheritance?
Dominant
* Women are affected
* Males more severely affected/lethal
Recessive
* Women are carriers and unaffected
* Men are always affected
* No male to male transmission
32
What are some general features of X-linked inheritance?
* X-linked genes never passed from father to son.
* All daughters of affected males are obligate carriers.
* Children of carrier females have a 50% chance of inheriting the mutant allele.
33
What is skewed X-inactivation?
* This occurs when all or most of the genes present on one of the two X chromosomes are silenced.
* The choice of which X chromosome is silenced is generally random but 10% of women have uneven or skewed X-inactivation - when inactivation of one X chromosome is favoured over the other.
34
Explain the concept of manifesting carriers
* When some women have some symptoms in X-linked recessive conditions
* Occurs as a result of X-inactivation silencing the genes on a healthy X-chromosome which would leave all the genes on the unhealthy X-chromosome to be expressed
35
What is Y-linked inheritance?
* When a trait/disorder that is produced by genes located on the Y chromosome are passed down to offspring
36
What are some features of Y-linked inheritance?
* Appears in all sons of males who exhibit that trait
* Is absent from daughters of trait carriers
37
What is the difference between a mutation and a pathogenic mutation?
* Mutation - A change in the structure of a gene
* Pathogenic mutation - A change in the structure of a gene that results in an alteration of the function of the gene product and can cause a disease phenotype
38
What are the different types of mutation?
* Substitutions
* Deletions
* Insertions
39
What are the different types of substitution mutation?
* **Synonymous substitution -** occurs when a change in a single base doesn’t change the amino acid sequence
**Missense substitution -** occurs when a change in a single base does change the amino acid sequence therefore changing the protein produced
**Nonsense substitution -** occurs when a premature stop codon is seen within a DNA sequence resulting in the production of an incomplete protein
40
What is an insertion mutation?
Insertion of a single nucleotide into a DNA sequence
41
What is a deletion mutation?
Deletion of a single nucleotide from a DNA sequence
42
What is meant when it is said that insertions and deletions can occur "in frame" or "in frameshift?"
* In frame - Insertion/deletion of bases in multiples of 3
* Frameshift - Insertion/deletion of bases not in multiples of 3 e.g. deletion of only 2 bases
Genomics
flashcards
Decks in class (18)
# Cards
-
DNA complementarity, hybridisation and its effects30
-
PCR and its roles in diagnostics25
-
Molecular Evolution36
-
Genome structure34
-
Genome variation32
-
Inheritance patterns42
-
Enzyme and restriction mapping42
-
Recombinant DNA and cloning vectors30
-
DNA Sequencing by Dideoxy-chain termination18
-
Linkage Analysis30
-
Microarrays36
-
Next generation sequencing24
-
The Metagenome25
-
The functional genome30
-
The Mitochondrial Genome35
-
The Epigenome31
-
Mapping Mendelian Disease28
-
Genetics of common disease32
