Genetic Principles

Question 1

1 chromosome contains

Answer 1

a single, continuous DNA double helix

Question 2

genetic polymorphism

Answer 2

genes exist in multiple forms (alleles)

Question 3

locus (plural loci)

Answer 3

the location of an allele on a chromosome

Question 4

wild type gene/allele

Answer 4

• common in most individuals

* contrast with mutant gene/allele

Question 5

germ line mutation

Answer 5

• in DNA of gametes

* found in every cell of offspring who receive mutant gamete

Question 6

somatic mutation

Answer 6

acquired in lifespan of cell -> not transmitted to offspring

Question 7

codominance

Answer 7

• both alleles contribute to phenotype

* classic example: AB blood type codominance

Question 8

Penentrance

Answer 8

proportion of individuals with an allele who express the phenotype for that allele

Question 9

incomplete penetrance

Answer 9

• not all individuals with the disease mutation develop the disease
• applied to autosomal dominant disorders

Question 10

BRCA1 and BRCA2 mutations

Answer 10

•germline, autosomal dominant mutation with incomplete penetrance

Question 11

expressivity

Answer 11

variations in phenotype of gene

Question 12

neurofibromatosis (NF1)

Answer 12

• brain tumors, skin findings
• autosomal dominant mutation with 100% penetrance
• but has variable severity (expressivity)

Question 13

pleiotropy

Answer 13

1 gene can cause 2 or more seemingly unrelated effects

Question 14

clinical examples of pleiotropy

Answer 14

• Phenylketonuria (PKU) -> skin, body odor, mental disability
• marfan syndrome -> limbs, eyes, blood vessels
• cystic fibrosis -> lungs, pancreas
• osteogenesis imperfecta -> bones, eyes, hearing

Question 15

“two-hit” origins of cancer

Answer 15

• a mutation in tumor suppressor gene
• heterozygous mutation -> NO disease
• mutation in both alleles -> cancer
• cancer requires 2 hits (often a germline mutation and a later developed somatic mutation to a tumor suppressor gene) -> “loss of heterozygosity”

Question 16

classic examples of tumor suppressor gene mutation cancers

Answer 16

• retinoblastoma
• HNPCC (lynch syndrome)
• familial adenomatous polyposis (FAP)
• Li-Fraumeni syndrome (gene for p53)

Question 17

mosaicism

Answer 17

• gene differences in cells of the same individual

* mutation in cells -> mixture of genetic makeup

Question 18

germline mosaicism

Answer 18

• can be passed on to offspring

* offspring disease will appear sporadic

Question 19

somatic mosaicism

Answer 19

• gene differences in tissues/organs
• not passed on to offspring
• examples: 45x/46xx turner syndrome (milder form), and rare forms of down syndrome

Question 20

McCune-Albright syndrome

Answer 20

• rare disorder
• precocious puberty (menarche as early as 2yo)
• fibrous growth in bones (-> fractures and deformity)
• skin: cafe-au-lait spots and irregular borders (“coast of maine”)
• example of somatic mosaicism (post-zygotic mutation) because germline occurances of this mutation will be lethal

Question 21

genetic heterogeneity

Answer 21

same phenotype can be caused from different genes or mutations

Question 22

allelic heterogeneity

Answer 22

•1 type of genetic heterogeneity
•different mutations within the same locus can cause the same disease
•one disease = multiple genes = single location
EX: beta thallasemia and cystic fibrosis

Question 23

locus heterogeneity

Answer 23

•1 type of genetic heterogeneity
•when different genes cause the same disease
•one disease = multiple genes = multiple locations
EX: retinitis pigmentosa (autosomal dominant, recessive, and x-linked forms)

Question 24

incomplete dominance (semidominance)

Answer 24

• heterozygote phenotype different from homozygote

* ie heterozygotes have less severe form of disease than homozygotes

Question 25

father to son transmission of disease indicates

Answer 25

an autosomal disease

Question 26

lyonization

Answer 26

• formation of barr body in females
• one x chromosome undergoes lyonization to become methylated -> heterochromatin
• random process -> different x chromosomes in different cells -> x mosaicism

Question 27

skewed lyonization

Answer 27

can lead to a female showing symptoms of an x linked recessive disorder while only having received one of diseased x chromosome

Question 28

key pedigree finding in x linked dominant disorders

Answer 28

every daughter of an affected male has the disease

Question 29

key difference between autosomal dominant and x linked dominant (pedigree)

Answer 29

x linked dominant can mimic autosomal dominant pattern, but the key difference is NO male-to-male transmission (fathers always pass y chromosome to son)

Question 30

x linked dominant disorder

Answer 30

• disease tends to be more severe among males

* classic example: fragile x syndrome

Question 31

organs most affected by mitochrondrial DNA mutations

Answer 31

•CNS
•skeletal muscle
(rely most heavily on aerobic metabolism)

Question 32

heteroplasmy

Answer 32

• multiple copies of mtDNA in each mitochondria and multiple mitochondria in each cell – can have a mix of normal and abnormal DNA
• rare, but if all normal or all abnormal -> homoplasmy

Question 33

significance of heteroplasmy

Answer 33

• mutant gene expression is highly variable

* depends on normal:abnormal genes in mitochondria and number of mutant mitochondria/cell or tissue

Question 34

mitochondrial disorder transmission

Answer 34

• homoplasmic mothers -> all children will have disorder
• heteroplasmic mothers -> variable
• affected fathers -> no transmission

Question 35

key of polygenic inheritance

Answer 35

does not follow mendelian inheritance patterns

Question 36

pedigree of a mitochondrial disorder

Answer 36

transmission occurs only through affected females, and never through males