Lecture 2: Mendelian and Non-Mendelian Genetics I

Question 1

Unit Inheritance

Answer 1

Parental phenotypes do not “blend” in offspring.

Question 2

Segregation

Answer 2

Genes exist in pairs; only one member of each pair is transmitted to offspring.

One of Mendel’s basic principles of heredity.

Question 3

Independent Assortment

Answer 3

Genes at different loci are transmitted independently. This is due to random recombination of maternal and paternal chromosomes.

One of Mendel’s basic principles of heredity.

Question 4

Mendelian Inheritance

Answer 4

Refers to the single gene transmission of inherited traits from generation to generation; not all inheritance follows these rules.

Question 5

Autosomal Dominant Inheritance

Answer 5

Only one copy of a mutant allele is necessary for the expression of an autosomal dominant trait.

Clinical characteristics:

• Variable Expressivity
• Incomplete Penetrance
• De novo mutations

Question 6

Variable Expressivity

Answer 6

The same genetic condition can present with different clinical symptoms at different ages and with varying degrees of severity–even within the same family.

E.g. hair color.

Question 7

Penetrance

Answer 7

The proportion of individuals heterozygous for a given autosomal dominant gene mutation who have any of the known phenotypic effects of the gene.

Question 8

Complete Penetrance

Answer 8

All heterozygotes known to have the gene for the condition have the phenotype.

Question 9

Reduced (Incomplete) Penetrance

Answer 9

Not all heterozygotes known to have the gene have clinical (phenotypic) features of the disorder.

Question 10

New (De Novo) Mutations

Answer 10

New gene mutations that can occur. Often found at “hot spots” in the genome.

Question 11

Autosomal Recessive Inheritance

Answer 11

Two copies of a mutant allele are necessary for expression of an autosomal recessive trait.

E.g. Cystic Fibrosis

Characteristics:

• Less expressive variability
• Penetrance is usually complete
• Ethnic predispositions, i.e. sickle cell

Question 12

X-Linked Recessive Inheritance

Answer 12

The mutated allele is on the X chromosome.

-E.g. Hemophilia

Characteristics:

• Male to male transmission not observed.
• All daughters of affected male are carriers
• Males much more likely to be affected

Question 13

Obligate Carrier

Answer 13

An individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history; usually applies to disorders inherited in an autosomal recessive and X-linked recessive manner.

Question 14

Lyonization

Answer 14

Only one X chromosome is active in each somatic cell of a female mammal. Inactivation usually occurs randomly in early embryonic life.

Any cells derived from affected cells with have the same inactivated X.

Question 15

Skewed (non-random) X-Inactivation

Answer 15

When the inactivation of one X chromosome is favored over the other in all cells of the body.

High ratios become medically significant, which can result in symptomatic carriers.

Symptomatic females tend to be less severely affected than males.

E.g. Duchenne MD

Question 16

X-Linked Dominant Inheritance

Answer 16

Only one copy of a mutant allele on the X-Chromosome is necessary for expression of an X-linked dominant trait, whether in a male or female.

Characteristics:

• Females are more likely to be affected.
• Much less common than X-linked recessive disorders.
• No male-male transmission

E.g. Incontinentia Pigmenti

Question 17

mtDNA

Answer 17

Mitochondrial DNA; encodes some of the subunits needed for the oxidative phosphorylation chain.

Most of the subunits are encoded by nuclear DNA, however.

Question 18

Heteroplasmy

Answer 18

Mixture of normal and abnormal DNA; usually refers to mtDNA.

Question 19

Homoplasmy

Answer 19

All DNA is the same (i.e. all normal or all abnormal); usually refers to mtDNA.

Question 20

mtDNA Segregation

Answer 20

Occurs randomly as the cell divides; mixtures of normal and abnormal separate in varying proportions.

Question 21

mtDNA composition changes over time by what mechanisms?

Answer 21

1. Chance variation (genetic drift).

2. Selective (replicative) advantage.

Question 22

Threshold Effect

Answer 22

A certain percentage of abnormal mtDNA molecules may be tolerated without symptoms. Once the threshold is reached, symptoms appear.

Threshold varies from tissue to tissue (think ATP needs) and person to person.

Question 23

What organ systems are likely to be affected by human mitochondrial disorders?

Answer 23

Those with large ATP requirements.

E.g. CNS, skeletal muscle, eye muscle, heart muscle.

Less commonly, GI tract, pancreas, bone marrow, ANS.

Question 24

Why are mitochondrial disorders difficult to identify and diagnose?

Answer 24

Heteroplasmy; random mixtures of normal and abnormal mtDNA in each mitochondria obscure identification.

Though it is theoretically possible, it is very difficult.

Question 25

How many copies of mtDNA do mitochondria have?

Answer 25

Hundreds, as opposed to two in the nucleus.

Question 26

Achondroplasia

Answer 26

A condition that is a good example of dominant inheritance. It is also known as dwarfism.

• 80% of all cases are de novo.
• 90% due to one of two mutations.

Question 27

Principles of Autosomal Dominant Inheritance

Answer 27

• Only one gene copy is necessary for expression.
• Multiple generations are affected, but can also be de novo.
• Male to male transmission observed.

(these are a few)

Question 28

Marfan Syndrome

Answer 28

A syndrome that has many varying symptoms with varying severity.

Cardinal manifestations are bone overgrowth, joint laxity, and cardiovascular pathologies.

A good example of “Variable Expressivity.”

Question 29

Non-Mendelian Inheritance

Answer 29

Any pattern of inheritance in which traits do not segregate in accordance with Mendel’s laws.

Examples:

• Mitochondrial
• Trinucleotide Repeats
• Mosaicism

Question 30

How does age affect mitochondrial function and why?

Answer 30

Function decreases.

Hypotheses:
-Damage to mtDNA from free radicals.

-Increased mutation rate due to a lack of repair enzymes

Question 31

Three Parent I.V.F.

Answer 31

Taking the nucleus of a mother out of an affected cell with mutant mtDNA and placing it into a de-nucleated cell with normal mtDNA.