Mendelian Inheritance and Pedigree Analysis

Question 1

Mendelian patterns of inheritance

Answer 1

Autosomal dominant
Autosomal recessive
X-linked

Question 2

Non-mendelian patterns of inheritance

Answer 2

Mitochondrial
Mosaic
Imprinted
Uniparental disomy

Question 3

Autosomal trait

Answer 3

On one of the 22 pairs of non-sex chromosome

Question 4

X-linked trait

Answer 4

on the x chromosome

Question 5

Holandric trait

Answer 5

on the y chromosome

Question 6

Sex-limited trait

Answer 6

only manifests in 1 sex

Question 7

Penetrance

Answer 7

proportion of people with a particular allele (genotype) who manifest the trait (phenotype)

Question 8

Expressivity

Answer 8

Severity-how present is the trait?

Question 9

Locus

Answer 9

the site on a chromosome where a gene is located

Question 10

Alleles

Answer 10

alternate forms of a gene at a particular locus; most genes have two alleles, one on each chromosome (except genes on sex chromosomes)

Question 11

Homozygous

Answer 11

both alleles the same

Question 12

Heterozygous

Answer 12

two alleles different

Question 13

Mendel’s first law

Answer 13

Independent segregation: transmission of each allele to offspring with equal frequency

Question 14

Mendel’s second law

Answer 14

Independent assortment: transmission of an allele at one locus is independent of transmission of alleles at other loci

Question 15

Why is assortment independent?

Answer 15

Meiotic recombination

Question 16

Pedigree symbols

Answer 16

• F = circle

- M = square

Question 17

Autosomal recessive traits

Answer 17

• Expressed only when both alleles are for trait (homozygous)
• “horizontal transmission” = many cases in one generation while family history negative
• M and F affected equally
• 25% risk in child from heterozygous parents

Question 18

How are carriers of autosomal recessive alleles identified?

Answer 18

Level of gene product (gene dosage) is half normal

Question 19

Describe the relationship between gene dosage and phenotype in autosomal recessive disorders.

Answer 19

• Heterozygotes have no clinical phenotype; level of gene product is not highly critical
• Homozygotes have complete enzyme deficiency and thus phenotype

Question 20

Examples of autosomal recessive disorders

Answer 20

• Hemoglobinopathies
• Tay-sachs
• CF
• Gaucher
• PKU
• Galactosemia
• Oculocutaneous albinism
• Infantile polycystic kidney disease
• Hurler

Question 21

Autosomal dominant traits

Answer 21

• Expressed when only 1 allele is for a trait (heterozygotes have phenotype)
• “vertical” transmission: anyone with the trait has a parent with the trait
• M and F equally affected
• 50% risk in child with affected parent
• if neither parent affected, child can have trait due to new mutation

Question 22

Examples of autosomal dominant disorders

Answer 22

• Marfan
• Neurofibromatosis
• Adult-type polycystic kidney disease
• Apert syndrome
• Osteogenesis imperfecta
• Achondroplasia
• Huntington

Question 23

Codominant traits

Answer 23

• Traits determined by both alleles expressed (neither dominant)
• Ex: ABO blood types

Question 24

X-linked recessive traits

Answer 24

• Usually in M (recessive, and F have two X’s)
• If mother carrier: 50% daughters carriers and 50% sons affected
• If father carrier: daughters all carriers and no sons affected

Question 25

X-linked recessive disorders

Answer 25

- Red-green colorblindness - G6PD deficiency - Hemophilia - Fragile-X - Duchenne muscular dystrophy

Question 26

X-linked dominant traits

Answer 26

- Expressed in M and F - No father -> son transmission - Mother with trait: 50% of sons and daughters with trait - Father with trait: all daughters affected, no sons affected

Question 27

Gene dosage and autosomal recessive disorders

Answer 27

- If one allele is defective (heterozygosity), half normal amount of gene product made - For most enzymes half is enough => homozygosity leads to disease

Question 28

Hemizygosity

Answer 28

- Males have only one X chromosome and thus only 1 allele | - Defect in this one allele can produce disease

Question 29

Lyonization

Answer 29

- Inactivation of one X chromosome in each cell early in development

Question 30

Allelic mosaicism

Answer 30

- Different cells express different X alleles in females as a result of lyonization - Females may be heterozygous overall but allelic expression is mosaic by cell or tissue

Question 31

Gene codominance

Answer 31

- Two alleles (WT and mutant) often expressed equally. | - Genes are not dominant or recessive! Phenotypes are

Question 32

Genetic fitness

Answer 32

- Capacity to procreate and pass on genes | - Requires survival to reproductive age

Question 33

Reconcile fitness and the presence of childhood lethal genetic disorders over generations.

Answer 33

- Recessive: asymptomatic carriers "fit" | - Dominant: occur due to new mutations

Question 34

Autosomal dominant disorders and genes prone to recurrent mutations

Answer 34

- Type 1 Collagen => osteogenesis imperfecta - Neurofibromin => neurofibromatosis - FGFR3 => achondroplasia (mutation risk increases with increased paternal age)

Question 35

Haldane rule

Answer 35

- Gene frequency for lethal x-linked disorders is stable because of new mutations which account for 1/3 of all new cases - Otherwise, we'd expect frequency to decrease over generations as affected males "aren't fit"

Question 36

Linkage analysis

Answer 36

Used to trace inheritance of a trait or disease by presence of a linked trait