Lecture 12 Flashcards
1
Q
Define genotype
A
genetic makeup
2
Q
What is a pedigree chart?
A
A pedigree is a diagram showing genetic information from a family, using standardized symbols
3
Q
State 2 purposes of a pedigree chart
A
- Determines whether the pattern of inheritance for a given trait
- Discovers whether the gene in question is located on an X or Y chromosome or an autosome
4
Q
Why is it important to establish how a trait is inherited?
State 3 reasons
A
If the pattern of inheritance can be established, it can be used to predict genetic risk in several situations, including:
- Pregnancy outcomes
- Adult-onset disorders
- Recurrence risks in future off spring
5
Q
Pedigrees use a standardised set of symbols.
How are males and females represented?
A
- Squares represent males
- Circles represent females
6
Q
Pedigrees use a standardised set of symbols.
How are affected individuals represented?
A
Individuals with the phenotype in question is represented by a filled-in symbol
7
Q
Pedigrees use a standardised set of symbols.
How are heterozygotes represented?
A
Heterozygotes, when identifiable, are indicated by a shaded dot or a half-filled symbol
8
Q
Pedigrees use a standardised set of symbols.
How are individuals represented when their sex is unknown?
A
If the sex of a person is unknown, a diamond is used
9
Q
Pedigrees use a standardised set of symbols.
How are romantic relationships represented?
A
- Parents are connected by a horizontal line
- Closely related parents (such as first cousins) are connected by a double line
- Divorced parents are connected by a horizontal line with slanted lines
10
Q
Pedigrees used a standardised set of symbols.
How are offspring represented?
A
- Offspring are connected to parents by a vertical line
- Off spring are connected by a horizontal sibship line (listed in birth order from left to right)
11
Q
Pedigrees used a standardised set of symbols.
How are twins represented?
A
- Non-identical twins are connected by two diagonal lines
- Identical twins are connected by two diagonal lines as well as a horizontal sibship line
12
Q
Pedigrees used a standardised set of symbols.
How are aborted, miscarried or stillborn offspring represented?
A
Deceased offspring are represented with a cross through their respective symbols
13
Q
Pedigrees used a standardised set of symbols.
How are deceased individuals represented?
A
Deceased individuals are represented with a diagonal line through their respective symbol
14
Q
Explain the numbering system in pedigree construction
A
- Each generation is identified by a Roman numeral (I, II, III, and so on)
- Each individual within a generation is identified by an Arabic number (1,2,3, and so on)
15
Q
What are the five basic Mendelian patterns of inheritance for traits controlled by single genes?
A
- Autosomal recessive inheritance
- Autosomal dominant inheritance
- X-linked dominant inheritance
- X-linked recessive inheritance
- Y-linked inheritance
16
Q
Identify a non-Mendelian pattern of inheritance
A
Mitochondrial inheritance - traits controlled by single genes coded for by mitochondrial genes
Polygenic - lots of characteristics are controlled by lots of genes
Complex or multifactoral - genes and the environment work together
17
Q
What effects inheritance?
A
Environment - can control genotype and phenotype. For example, DNA damage by radiation
18
Q
Which diseases are more to do with genotype and which diseases are more to do with environment?
A
Mix between genotype and environment (controlled by both genotypes and environment - both are important)
19
Q
Identify 3 unique features of autosomal recessive inheritance
A
- All the children of two affected (homozygous) individuals are affected
- The risk of an affected child from two heterozygote parents is 25%
- For rare traits, affected individuals have unaffected parents (can skip generations due to carriers)
- Disease can seem to ‘come out of nowhere’
- Males and females equally affected
20
Q
What can be expected with traits on autosomes (non-sex chrosomes)?
A
- Expressed in both males and females (affected in roughly equal numbers)
- Both the male and the female parent transmit the trait
21
Q
Identify 6 different diseases with autosomal recessive inheritance
A
- Albinism
- Cystic fibrosis
- Phenylketonuria
- Sickle cell anaemia
- Thalassemia
- Xeroderma pigmentosum
22
Q
Draw out a diagram showing the inheritance of autosomal recessive?
A
23
Q
Draw out an example of an autosomal recessive punnett square
A
24
Q
Autosomal dominant (features of this)
A
- Males and females equally affected
- Every affected individual will have (at least) one affected parent
- Disease cannot skip a generation, i.e. affected individual(s) found in every generation
25
Identify 4 unique features of autosomal dominant inheritance
- Most affected individuals are heterozygotes and still have an abnormal phenotype
- Unaffected individuals carry two recessive alleles
- All offspring have a 50% chance of being affected
- Every affected individual has at least one affected parent
- AUTOSOMAL DOMINANT DISEASES ARE RARELY FOUND IN HOMOZYGOUS STATE - THEREFORE ASSUME THAT INDIVIDUALS ARE HETEROZYGOTES (as the zygote wouldn't survive if there are two alleles)
26
Briefly, describe the features of the following clinical conditions:
- Albinism
- Cystic fibrosis
- Xeroderma pigmentosum
- **Albinism:** absent pigments in skin, eyes, hair
- **Cystic fibrosis:** mucous production that blocks the ducts of certain glands and lung passages
- **Xeroderma pigmentosum:** lack of DNA repair enzymes leading to UV light sensitivity and skin cancer
27
Briefly, describe the features of the following clinical conditions:
- Phenylketonuria
- Sickle cell anaemia
- Thalassemia
- **Phenylketonuria**: excess accumulation of phenylaline in blood leading to mental retardation
- **Sickle cell anaemia:** abnormal haemoglobin leading to blood vessel blockage (crises)
- **Thalassemia:** improper haemoglobin production with symptoms ranging from mild to fatal
28
How can one differentiate between homozygous and heterozygous patients for autosomal dominant disorders?
- Phenotype in homozygous dominant individuals is often **more severe**
- Homozygous dominant trait is often **not compatible with life**
29
Describe the relationship with homologous chrosomes and chromatids
* Homologous chromosomes have the same genes
* Homologous chromosomes may carry different alleles
* Sister chromatids have identical DNA, have the same alleles
* Non-sister chromatids have the same genes, but may have different alleles
30
An individual with an autosomal dominant disorder has two unaffected parents. How did this disorder occur?
- A mutation occured in single gene
- Common for genes with high mutation rates
31
Identify 4 different diseases with autosomal dominant inheritance
- Achondroplasia
- Ehlers-Danlos syndrome
- Marfan syndrome
- Huntington disease
32
Briefly, describe the features of the following clinical conditions:
- Achondroplasia
- Marfan's syndrome
- **Achondroplasia**: dwarfism associated with defects in growth regions of long bones
- **Marfan syndrome:** connective tissue defect due to mutation in fibrillin gene, individuals are incredible tall & lanky
33
Briefly, describe the features of the following clinical conditions:
- Ehler-Danlos syndrome
- Huntington's disease
- **Ehlers-Danlos syndrome:** connective tissue disorder presenting with elastic skin and loose joints
- **Huntington disease:** progressive degeneration of nervous system, resulting in dementia and early death
34
X-linked recessive chromosomes
35
Example of an X-linked recessive punnett square
36
What is sex-linked inheritance?
- **Sex chromsomes** are the X and Y chromosomes
- Genes on the X chromosome are called **X-linked**
- Genes on the Y chromosome are called **Y-linked**
37
Describe paternal inheritance - genes on the Y chromosome
- Only males have Y chromosomes, hence, traits encoded by Y genes are passed directly from father ⇒ son
- All Y-linked traits should be expressed because males are **hemizygous** for all genes on the Y chromosome
38
What does it mean to be hemizygous for genes on sex chromosomes?
- Males cannot be homozygous or heterozygous for both X-linked and Y-linked geness
- A gene present on either the X/Y chromosome is expressed in males in both the recessive and dominant forms
39
Identify 3 unique features of X-linked dominant inheritance
- Affected males transmit the trait to all their daughters but none of their sons.
- An affected heterozygous female will transmit the trait to half of her children (both genders affected equally)
- On average, twice as many females are affected as males (females can be heterozygous or homozygous)
40
Identify 4 unique features of X-linked recessive inheritance
* Males and females unequally affected
* Every affected (hemizygous) male will have (at least) a heterozygous carrier mother
* Every affected female will have an affected father and a carrier mother
* Affected males will have (at least) heterozygous daughters
WHENEVER SEE MALES MORE AFFECTED THAN FEMALES - THINK X-LINKED
41
Why are far more males affected by X-linked recessive genetic disorders than are females?
- Females have two X chromosomes and, hence, can be heterozygous or homozygous for any X-linked genes
- Males only carry only one copy of the X chromosome hence are **hemizygous** for X-linked genes
- Males **have no dominant X allele to mask expression** of the recessive X allele
42
Y-linked
* Only males affected
* Affected males will give trait to all their sons
* Y-linked diseases always linked to ‘maleness’
43
Identify 3 unique features of maternal mitochondrial inheritance
- All individuals will inherit their mitochondrial DNA from their mother
- All the children of affected females are affected
- Affected females transmit the trait to all their offspring
- Affected males do not transmit the trait to offspring
44
Why do mitochondrial genes follow a maternal inheritance?
- Mitochondria are transmitted from mothers to all their children through the cytoplasm of the egg
- Sperm do not contribute mitochondria at fertilization
45
Outline the effects of mitochondrial disorder
- Mutations in mitochondrial genes reduce the amount of energy available for cellular functions
- Phenotypic effects are highly variable and generally affect tissues with the highest energy demands (muscles & nervous system)
46
What is the name given to mitochondrial disorders which affect mainly muscles?
Mitochondrial myopathies
47
What is the name given to mitochondrial disorders which affect both muscles and the nervous system?
Mitochondrial encephalomyopathies
48
Polygenic inheritance
More than one gene can be involved in producing a phenotype
(in example below - 3 enzymes from different genes, if one goes wrong, doesnt form final product)
49
Principles of polygenic inheritance
* Genes on the same chromosome are said to be ‘linked’
* Genes on different chromosomes are said to be ‘not linked’
* Linked genes do not show independent assortment at meiosis…
50
Polygenic inheritance
Albinism is inherited in a recessive manner two genes? 2 genes A1 and A2, each with 2 alleles A1,a1, A2, a2
51
Polygenic inheritance (not-linked)
52
Polygenic inheritance (linked)
53
Discuss polygenic inheritance and linked genes (more likely in certain positions etc...)
* Linked genes do not show independent assortment at meiosis
* Recombination frequency between two linked genes is dependent on the distance between the genes
* Linked genes close together are ‘tightly linked’
* Linked genes far apart on the same chromosome almost behave as unlinked genes
- In the picture, crossing over between A and E are unlikely, more likely to have crossing over between A and D
54
55
Define homozygous
two alleles of a gene are the same individual is a homozygote
56
Incomplete dominance does not follow predicted ratios for a Mendelian trait.
Illustrate this using an example
**- Incomplete dominance** is the expression of a phenotype that is intermediate to those of the parents
- This involves a distinctive phenotype in heterozygotes:
57
Codominance does not violate the expectations of Mendel’s laws.
What is this phenomenon?
- **Codominance** is when both alleles in a heterozygote are fully expressed
- The expected Mendelian genotypic ratio of 1:2:1 is observed
58
Explain the phenomenon of multiple alleles
- Many genes have more than two alleles (**multiple alleles**)
- An individual can carry only two alleles of a gene but members of a population can carry many different alleles of a gene
* E.g. blood groups*
59
Define phenotype
Phenotype: characteristics
60
Describe the relationship with genes and alleles
* Each human has approximately 25,000 genes
* Each individual has two copies of each given gene
* Each individual has two alleles of a gene
* BUT there are many alleles of a gene within a population!
61
Explain the phenomenon of epistasis
- **Epistasis** is the interaction of two or more non-allelic genes to control a single phenotype
- The action of one gene masks or prevents the expression of another gene *e.g. Bombay phenotype*
62
What is the Bombay phenotype?
- The **Bombay phenotype** is when a mutation in a the h gene prevents the expression of the A and B phenotypes
- Individuals homozygous for a recessive allele **h** are blocked from expressing the A or B surface antigen
- They are phenotypically blood type O, even though genotypically carry IA / IB alleles
63
Explain mendelian inheritance by independent assortment
- The inheritance of two traits in humans follows the principle of independent assortment
- Gametes independently assort themselves during metaphase of meiosis increasing the variation in offspring
64
What is a proband?
A **proband** is the first affected family member who seeks medical attention for a genetic disorder (indicated by an arrow)
65
Define gene
a stretch of DNA sequence at a specific chromosomal location that carries the code for a polypeptide or untranslated RNA (plus regulatory sequences)
66
Define allele
a version or variant of a gene
67
Autosomal recessive
* Heterozygotes unaffected
* Affected individuals are homozygous recessive
* Two affected individuals will only have affected offspring
* Two heterozygotes (carriers) have 25% chance of having affected offspring
e.g. D d
D DD Dd
d Dd dd dd is cystic fibrosis
68
Define heterozygous
two alleles of a gene are different individual is a heterozygote
69
Hemizygous
only one allele of a gene on the X chromosome
70
Define dominant
the dominant allele in a heterozygote determines the phenotype
71
Define recessive
the non-dominant allele in a heterozygote is called recessive
72
Co-dominant
• neither allele in a heterozygote is dominant and the phenotype is new (different from the phenotypes determined by either allele)
73
Human blood types phenotypes
Look at attached...
The type of antigen e.g. blood group A is the phenotype (it has antigen A on)
74
Human blood genotypes
(A is dominant over O, B is dominant over O, A and B are co-dominant)
75
How are the blood type codes written?
* Human ABO gene is located on chromosome 9 (9q34.2) and codes for glycoproteins on the surface of red blood cells (don't need to know specific chromosomal locations)
* the gene is often written abbreviated as I (isoagglutinogen)
* the gene has three alleles A, B and O or IA , IB and IO (this means gene I, and then allele A, B or O)
* allele A and allele B are dominant over allele O
* allele A and allele B are co-dominant
76
Draw out a diagram showing an example of mothers and fathers chromosomes passing on autosomal recessive
77
Autosomal dominant - would can you assume about a phenotype with the disease?
Can assume that all affected individuals are heterozygotes (as they don't come in the homozygous form)
78
Hardy Weinberg
79
Twins (identical and non-identical)
- monozygotic (identical)
- dizygotic (non-identical)
