Inheritance Patterns Flashcards
What is the symbol for a male on a pedigree?
→ A square
What is the symbol for a female on a pedigree?
→ A circle
How do you show that two people are partners on a pedigree?
→ There is a line between them
How do you show children on a pedigree?
→ There is a line down
How do you show siblings on a pedigree?
→ There is a line above connecting them from the top
How do you show affected people on a pedigree?
→ They are colored in
How do you show carriers on a pedigree?
→ A shaded dot within the shape
How do you show a consanguineous couple on a pedigree?
→ A double line joining them
What is a stillborn baby of unknown sex on a pedigree?
→ A rhombus with the SB symbol
How is a spontaneous abortion shown on a pedigree?
→ a triangle
How is a therapeutic abortion shown on a pedigree?
→ A triangle with a line through it diagonally
How are twins shown on a pedigree?
→ two shapes coming from the same vertical line
How is pregnancy shown on a pedigree?
→ A rhombus with a P inside it
What is a rhombus on a pedigree?
→ Unaffected person whose sex is unknown
How do autosomal dominant conditions manifest?
→ Heterozygous form
What are the 4 key things to look for in an autosomal dominant pedigree?
→ Multiple generations affected
→ Both sexes
→ Male to female and female to male transmission
→ Most will have an affected parent
→ If both parents possess the trait, but it is absent in any of their offspring, then the parents are both heterozygous (“carriers”) of the recessive allele
How do you know that an autosomal dominant condition is not carried on the sex chromosome?
→ Both genders are affected
→ Transmission between sexes
What is the risk for each child of an affected parent with an autosomal dominant condition?
→ 50% risk
What is penetrance?
→ % of individuals who carry the mutation and develop symptoms of the disorder
What does a 75% penetrance mean?
→ Someone can have the dominant allele but not phenotypically have the disease
→ Huntingtons
What is variable expressivity?
→ Variation in the severity/symptoms of the disorder
What is a condition that exhibits variable expressivity?
→ Neurofibromatosis I
What is somatic mosaicism?
→ New mutation arises at an early stage of embryogenesis
→ Present in some tissues or cells
→ If the majority of cells are not affected then the disease severity is reduced
What is germ line mosaicism?
→ New mutation arises during oogenesis or spermatogenesis
→ Mutation present in variable proportion of gametes
→ Some gametes will have the mutation and some will not
Which type of mosaicism can be transmitted to offspring?
→ Germ line mosaicism
What is anticipation and what kind of disorders does this occur in?
→ Worsening of the disease severity in successive generations
→ occurs in triplet repeat disorders
How do autosomal recessive conditions manifest?
→ Homozygous
→ Compound heterozygous
What are the key things to look for in an autosomal recessive pedigree?
→ Carriers (heterozygote) not affected
→ Both sexes affected
→ One generation affected
→ can be consanguinity
→ Affected individual does not have affected parents
What is a compound heterozygote?
2 mutations are in the same gene
→ Mutations are different
Vast majority of recessive is compound heterozygosity
What is a homozygote?
→ 2 mutations in the same gene
→ Identical mutations
What is an example of different mutations in genes in a compound heterozygote? (cystic fibrosis)
→ delta F508
→ G542X
What is an example of the same mutation in genes in a homozygote? (cystic fibrosis)
→ Delta F508
→ Delta F508
What are features of autosomal recessive inheritance?
→ Found in clusters of siblings but not in parents and offspring
→ All offspring of affected person are obligate carriers
What is the carrier probability for autosomal recessive inheritance?
→ 2/3 for unaffected siblings of affected person
What is the recurrence risk for autosomal recessive inheritance?
→ 1/4 for each sibling of the affected person
What are the 2 features of X linked recessive inheritance?
→ Women are unaffected carriers
→ no male to male transmission
Hemizygous- loci on X-chromosome in men
What are the 2 features of X linked dominant inheritance?
→ Women are affected
→ Males are more severely affected/lethal
Why can women be homo or heterozygous for X linked inheritance?
→ They have 2 copies of the X chromosome
Why can men not be homo or heterozygous?
→ They only have a single copy of the X linked gene
How are X linked genes never passed?
→ never passed from father to son
What are all daughters of affected males with an X linked inheritance?
→ obligate carriers
What is skewed X inactivation?
→ The majority of genes on a woman’s X chromosome are inactivate
→ One of the X chromosomes are inactivated in all the cells
→ The healthy X chromosome is switched off more often than not so the mutated protein is expressed
What is an example of manifesting carriers in X linked disorders?
→ Some women have symptoms
→ Cardiomyopathy in DMD (Duchenne muscular dystrophy)
What is Y linked inheritance always passed from and to and what is an example of this?
→ Father to son
→ Hirsutism
What is a mutation?
→ A change in genetic material
What is a pathogenic mutation?
→ results in an alteration of the function of the gene product which causes a disease phenotype
What are 3 types of mutations?
→ Substitutions
→ Deletions
→ Insertions
What is a silent/synonymous change?
→ A nucleotide change without an amino acid change
What is a missense mutation?
→ Replacement of a single nucleotide
→ Incorrect amino acid gets produced
What is the impact of amino acid substitution?
Physiochemical similarity between two amino acids
→ Functional role of a specific domain of protein
→ Phylogenetic conservation of amino acid amongst diverse species
What is a nonsense mutation?
→ Replacement of a nucleotide
→ Stop codon is produced
→ Shortening of protein
What does an insertion mutation do?
→ Incorrect amino acid sequence
What types of insertion are there?
→ In frame (multiple of 3)
→ Frameshift (not a multiple of 3)
What types of deletion are there?
→ In frame (multiple of 3)
→ Frameshift (not a multiple of 3)
What do most autosomal dominant disorders show?
age-dependant penetrance. As one gets older, they show symptoms. BRCR 1 breast cancer
What is reduced penetrance?
Reduced penetrance- individuals carry mutation but do not show symptoms
Why are frameshift deletions more dangerous than in-frame?
extremely likely to lead to large-scale changes to polypeptide length and chemical composition, resulting in a non-functional protein that often disrupts the biochemical processes of a cell.
