Genen Flashcards
Who is the Proband?
the person who brings the family to the attention of the genetics clinic
Who is the Consultand?
the person sitting in front of you asking for genetic advice
Vertical pattern of inheritance
feature in which multiple generations are affected
This is dominant inheritance – you only need one faulty gene to get the disease
Horizontal inheritance
People in a single generation are affected (sibship)
This is recessive inheritance – you need two faulty genes to get the disease
NB: vertical always takes precedence over horizontal
Knight’s move inheritance
two males are affected through an unaffected
female
This is characteristic of an x-linked recessive disorder (the female has an additional
unaffected X chromosome which ‘protects’ her)
What is the inheritence of Achondroplasia?
Autosomal dominant
Causes short stature due to shortening of the limbs (short-limb dwarfism)
Shows complete penetrance
What is the inheritence of Albinism?
Autosomal recessive
Autosomal Dominant Inheritance
The genes for these traits are on the autosomes.
you need only one mutant gene to express the trait.
heterozygote and homozygote for the mutation show the same phenotype.
What are the features on a pedigree that suggest dominant inheritance?
1) vertical pattern of inheritance, affects every generation
2) both males and females affected
3) male to male transmission
Variable expression and complete/incomplete penetrance are possible
Variable expressivity
quantitative and qualitative differences in phenotype between individuals having the same allele or genotype.
I.e. not everyone affected, even in the same family (who are assumed to have
the same mutation) has exactly the same phenotype as they can be affected to different extents by the same gene.
severity, frequency of ‘attacks’ and age of onset can all vary.
What causes Variable expressivity?
Environmental factors causing an epigenetic effect (switching on or off of genes)
MODIFIER GENES: alter expression of a human gene at anotherlocusthat in turn
causes agenetic disease
If the trait is X linked, there can be variation due to the differences in the pattern of X inactivation
Incomplete penetrance
Refers to the fact that you can inherit a mutation, e.g. BRCA, but not express the phenotype
i.e. the phenotype can skip a generation
Many autosomal dominant disorders show incomplete penetrance
Obligate heterozygotes
individuals in the direct line of descent of an affected parent who have
affected children.
I.e. they must be carriers of the trait
GONADAL MOSAICISM
Gonadal mosaicism = a type of genetic mosaicism where more than one set of genetic information is found
specifically within the gamete cells.
When present in the gonads, offspring can inherit the mutation (will affect 100% of child’s cells)
Genetic mosaicism
Genetic mosaicism indicates that a person is composed of more than one genotype
develops when a genetic mutation occurs after fertilization, and results in an individual possessing both a mutated cell line and a normal cell line
Autosomal recessive conditions
for someone to be affected they must have inherited two faulty copies of the gene
Parents are assumed to be carriers
What are the characteristic traits of an autosomal recessive inheritance pattern?
1) horizontal pattern of inheritance
2) both sexes can be affected
3) parents are usually both carriers but unaffected
4) the probability of a normal sibling being a carrier is 2/3
5) if the trait is rare, there may be consanguinity
AR conditions are usually fully penetrant
What is the probability of a normal sibling of an affect child with an AR condition being a carrier?
2/3
What is the recurrence risk for each sibling of an affected person with an AR condition?
1/4 (25%)
Name 3 AR conditions
- sickle cell disease
- cystic fibrosis
- phenylketonuria (PKU)
- spinal muscular atrophy (SMA)
- congenital adrenal hyperplasia
Compound heterozygotes
have two different mutations in the same gene, causing a mutation in each allele
Sex linked inheritance
refers to traits controlled by genes on the X or Y chromosome.
Transmission of x-linked recessive disorders to offspring
1) XR traits show no male to male transmission since their sons receive their Y and not their X.
2) Unaffected males do not transmit the phenotype.
3) All daughters of an affected male are heterozygous carriers since they get their father’s X
chromosome with the mutant allele.
4) knights move pedigree pattern
4) males affected more than females
What is the genotype of the daughter of a man affected by an x-linked recessive disorder?
All daughters of an affected male are heterozygous carriers since they get their father’s X chromosome with the mutant allele.
What is the genotype of the son of a man affected by an x-linked recessive disorder?
XR traits show no male to male transmission since their sons receive their Y and not their X.
What is a manifesting carrier?
Females may be mildly affected x-linked recessive disorders as a result of to skewed x-inactivation (uneven inactivation of the x-chromosome)
What is the inheritance pattern of Duchenne Muscular Dystrophy?
X-linked recessive
~ 2/3 cases are inherited from a person’s mother
~1/3 cases are due to a new mutation
What is the risk of the son of a female carrier of an x-linked recessive disorder being affected?
Sons of female carriers have a 50% risk of being affected
father passes on Y chromosome, mother can pass on either the normal
X chromosome or the faulty X chromosome
What is the risk of the daughter of a female carrier of an x-linked recessive disorder being affected?
Females are usually only carriers
Daughters of a female carrier have a 50% chance of being a carrier
What are the expected genotype proportions of the offspring of a male with an X-linked recessive condition?
No sons are affected – passes on Y chromosome
all daughters are carriers
X-Linked Dominant Inheritance
When the disorder nearly always manifests in heterozygous females
Females tend to be affected twice as often as males and an affected female will transmit the phenotype
to 50% of her children independent of their sex.
No male to male transmission.
Name 3 conditions that show X-Linked Dominant Inheritance
vitamin D resistant rickets
Incontinentia pigmenti (has male lethality)
Rett syndrome (male lethality - usually)
What is the risk of the daughter of a female affected by an x-linked dominant disorder being affected?
50% chance of passing on the gene
Sons and daughters at equal risk
What is the risk of the son of a female affected by an x-linked dominant disorder being affected?
50% chance of passing on the gene
Sons and daughters at equal risk
What is the risk of the daughter of a male affected by an x-linked dominant disorder being affected?
All daughters will be affected
What is the risk of the son of a male affected by an x-linked dominant disorder being affected?
No sons will be affected
Which one of the following is common for X-linked recessive inheritance:
- Severely affected females
- Parental consanguinity
- Daughters are carriers if their father is affected
- Equal sex ratio for affected individuals
- Affected boys with an affected father
Daughters are carriers if their father is affected
What is Genetic “anticipation”?
Increasing severity and earlier age of onset of a condition in successive generations
Which conditions show genetic anticipation?
Huntington disease (HD),
Fragile X syndrome,
Myotonic dystrophy
what is Pseudo-dominant inheritance?
If an autosomal recessive condition has a very high carrier frequency or consanguinity – it appears like an autosomal dominant condition
i.e. the inheritanceof a recessive trait mimics adominant pattern
Which condition shows Pseudo-dominant inheritance?
Gilbert syndrome - carrier frequency is approximately 50%
What is the pattern of mitochondrial inheritance?
inherited only from the mother, but to variable extents
