Genetics:Pedigrees and Risk

Question 1

What are the main points for using a genetic pedigree?

Answer 1

Provides a clear simple summary of information
Able to spot patterns easily
Explain pattern to patient
Calculate the risk of passing on disease or being a carrier
Allows informed choice

Question 2

How are generations denoted on genetic pedigree?

Answer 2

Using roman numerals

Question 3

How are offspring birth ordered traditionally on genetic pedigrees?

Answer 3

Left tor right, individuals denote by Arabic numerals.

Question 4

Conventionally, which side is paternal lineage and maternal lineage denoted on a genetic pedigree?

Answer 4

Paternal - right

Maternal - left

Question 5

In relation to the proband which % of DNA is shared between grandparents?

Answer 5

25%

Question 6

In relation to the proband, which % of DNA is shared between parents?

Answer 6

50%

Question 7

In relation to the proband, which % of DNA is shared between siblings?

Answer 7

50%

Question 8

In relation to the proband, which % of DNA is shared between Aunts & uncles?

Answer 8

25%

Question 9

In relation to the proband, which % of DNA is shared between 1st degree cousins?

Answer 9

12.5%

Question 10

What is classified as consanguineous mating?

Answer 10

Mating occurs if 2nd cousins or closer (3.13% shared DNA)

Question 11

What pattern is provided by autosomal dominant conditions on a genetic pedigree?

Answer 11

Vertical transmission
The tendency for not all offspring expressing the conditions
Both genders are affected
Minimum of one parent required.

Question 12

Why are some familial disorders not expressed within the pedigree?

Answer 12

Have an age of onset, developing with age due to an accumulation of sporadic mutations
Deceased patients may not develop the disease, thus not expressed within the pedigree

Question 13

Which trinucleotide repeat causes Huntington’s?

Answer 13

CAG

Question 14

What inheritance pattern is demonstrated by Huntington’s?

Answer 14

Monogenic autosomal dominant disorder

Unstable mutation confers for a variable number of repeats

Question 15

How many CAG repeats cause full penetrance?

Answer 15

40+

Question 16

How is mitochondrial inheritance conferred?

Answer 16

The mutated gene is present in the mitochondrial DNA of the ovum; subsequent.y mtDNA is exclusively inherited from maternal lineages

Question 17

Which lineage has a strong inheritance pattern of mitochondrial DNA?

Answer 17

Maternal lineage

Question 18

What type of transmission pattern is evident for mitochondrial DNA inheritance?

Answer 18

Vertical transmission

Affects all generations,both genders are affected since the mutated gene is inherited from the mother

Question 19

What are the complicating factors of mitochondrial inheritance in terms of genomes and mt number?

Answer 19

Have multiple copies of genome ,therefore a proportion express normal genotype and mutant genotype
Offspring inherit varying numbers of mutated mitochondria this can change with time

Question 20

What is the pattern of inherited mitochondrial disease and age? Explain

Answer 20

Diseases develop with age due to accumulation of mutated mitochondria

Question 21

How do mitochondria replicate?

Answer 21

Binary fission

Question 22

What is the definition of genetic risk?

Answer 22

Risk is the calculation of the predicted chance of having the disease or being a carrier
Risk can only be calculated based upon the known phenotype to subject
Multiplication of risks to calculate overall risk of inheriting genetic disorder

Question 23

What are risk modifiers in terms of phenotypic advantage?

Answer 23

The lineages of the disease prevalence (maternal or paternal); X-linked and mitochondrial inheritance patterns
Ethnic background: Diseases have different prevalence in different populations
Example: CF, Sickle cell, Tay-Sachs
Whereby the heterozygous express a phenotypic advantage within the environment, the allelic frequency would increase within areas of relatively higher selection pressure
Founder effect

Question 24

What is the founder effect?

Answer 24

Due to a genetic bottleneck, also produced sub-populations with increased prevalence

Question 25

Which inheritance pattern is demonstrated by hereditary hemochromatosis?

Answer 25

Autosomal recessive disorder

Question 26

Which protein is the hereditary hemochromatosis allele affecting?

Answer 26

Homeostatic iron regulatory protein (HFE)

Question 27

What effect happens due to dysfunctional HFE protein?

Answer 27

Excess iron absorption