10: Genetic Disorders Definitions

Question 1

Penetrance in single gene mutations, complex multigenic disorders, and chromosomal disorders

Answer 1

Single gene and chromosomal disorders: high penetrance

Complex multigenic disorders: low penetrance

Question 2

Name six examples of autosomal dominant conditions

Answer 2

1. Huntingtons
2. Neurofibromatosis
3. Marfan’s
4. Ehler’s-Danlos
5. Osteogenesis imperfecta
6. Familiar hypercholesterolemia

Question 3

Name three examples of autosomal recessive conditions

Answer 3

CF, PKU, a1-antitrypsin deficiency

Question 4

Name two X-linked conditions

Answer 4

G6PD deficiency, fragile X syndrome

Question 5

Germ cell vs somatic cell mutation

Answer 5

Germ cell -> inherited disease

Somatic cell -> cancer, some congenital malformations

Question 6

Missense vs nonsense point mutation

Answer 6

Missense: changes to a different AA
Nonsense: changes to a stop codon

Question 7

When can mutations in noncoding sequences be bad?

Answer 7

When it causes failure to form mRNA

Question 8

Anticipation

Answer 8

As a genetic disorder is passed to the next generation, the sx become apparent at an earlier age with each generation (severity typically increases too)

Question 9

What does congenital mean?

Answer 9

“Born with” - doesn’t imply genetic

Question 10

Codominance

Answer 10

Both alleles contribute to a phenotype

Question 11

Pleiotropism

Answer 11

Single mutant gene -> many end effects

Question 12

Genetic heterogeneity

Answer 12

Mutations at several loci may produce same trait

Question 13

Incomplete penetrance

Answer 13

Mutation is present but normal phenotype

Question 14

Variable expressivity

Answer 14

All pts have trait, but are expressed differently

Question 15

Example of variable expressivity

Answer 15

Neurofibromatosis: +/- cafe au lait spots, skeletal deformities, neurofibromas

Question 16

What type of genetic transmission are almost all IEMs?

Answer 16

Autosomal recessive

Question 17

Genetic transmission of Ehlers-Danlos

Answer 17

Some autosomal dominant, some recessive

Question 18

If an autosomal recessive mutation is low frequency in a population and a child has it, what is most likely?

Answer 18

Consanguineous marriage

Question 19

Two diseases that are sulfatidoses

Answer 19

Gaucher dz, Niemann-Pick dz

Question 20

Condition that is a sphingolipidose

Answer 20

Tay-Sachs dz

Question 21

Example of how we know environmental contributions play a huge role in complex multigenic disorders

Answer 21

Dramatic reduction in neural tube defects by taking folic acid

Question 22

Why is it sometimes difficult to distinguish between single gene and multifactorial disease?

Answer 22

Single gene: variable expressivity and reduced penetrance

Complex multigenic: a range in severity level, which can be seen as variable expressivity and reduced penetrance

Question 23

Euploid

Answer 23

Any exact multiple of haploid number (23)

Question 24

Why are there no survivable monosomies?

Answer 24

Cause loss of too much genetic info -> cant even complete embryogenesis

Question 25

Two incidences where Robertsonian translocation occurs

Answer 25

1. In 1 in 1000 normal individuals

2. 3-4% of trisomy 21 cases

Question 26

How does inactivation of an X chromosome happen during lyonization

Answer 26

One X chromosome undergoes heteropyknosis at random on about day 5.5 of embryonic life -> all cells derived from these precursors will have that X chromosome inactivated

Question 27

True vs pseudohermaphrodite

Answer 27

True: presence of both ovarian and testicular tissue
Pseudohermaphrodite: disagreement between phenotype and gonadal sex

Question 28

Heteroplasmy

Answer 28

Tissue and individuals harbor both wild-type and mutant mtDNA

Question 29

Threshold effect

Answer 29

Minimum number of mutant mtDNA must be present in a cell or tissue before dysfunction gives rise to disease

Question 30

Five indications to have prenatal testing done

Answer 30

1. Advanced maternal age
2. Parent known to carry a balanced chromosomal rearrangement
3. Fetal anomaly on US
4. Routine maternal blood screen indicating increased risk of a trisomy
5. Children at known risk for many other genetic disorders

Question 31

How to obtain cells for prenatal testing

Answer 31

Amniocentesis, chorionic villus biopsy, umbilical cord blood

Question 32

New technology in prenatal testing

Answer 32

About 10% of free DNA in a pregnant mother’s blood is of fetal origin

Question 33

Proband

Answer 33

Affected individual

Question 34

COD for most CF patients

Answer 34

COPD

Question 35

In 95% of trisomy 21, where is the extra chromosome from?

Answer 35

Maternal origin

Question 36

Only way to establish a dx of 22q11.2

Answer 36

FISH to analyze the chromosomes