Genetics

Question 1

What is a genome?

Answer 1

• Complete set of genetic information, all the biologic information needed to build and maintain an organism
• Comprises all of the organism’s DNA

Question 2

What is an exome?

Answer 2

• Protein coding portion of DNA

- ~1% of total genome

Question 3

What is an intron?

Answer 3

• Non-coding sections of a gene

- Important biologic functions

Question 4

What is a nucleotide?

Answer 4

• Nitrogen-containing base (A and G are purines; T and C are prymidines)
• Sugar
• Phosphate
• Nucleotide strand forms a spiral (double helix)

Question 5

What is DNA transcription?

Answer 5

• mRNA takes coding to ribosomes where amino acids are formed
• Each tri-nucleotide sequence = codon
• 20 types of amino acids (each specified by codons)

Question 6

What are amino acids?

Answer 6

• Building blocks of proteins
• Sequenced, linked to form proteins
• Order of amino acids dictates protein shape and function
• Proteins play a critical role in the body

Question 7

What is a mutation?

Answer 7

-Change in a gene’s biochemical makeup, change at the DNA level

Question 8

What is a mutagen?

Answer 8

• A substance that causes a mutation

- EX: raidation

Question 9

What is a mutant?

Answer 9

-An allele that differs from the mild type (normal or most common) allele, altering the phenotype

Question 10

What is a spontaneous mutation?

Answer 10

-A genetic change resulting from the mispairing of bases during replication

Question 11

What is a mutational hot spot?

Answer 11

-Most likely to happen when the nearby DNA is repetitive or symmetrical

Question 12

What is a point mutation?

Answer 12

-Involving a single nucleotide in the DNA molecule

Question 13

What is a missense mutation?

Answer 13

• Change in a codon so that it codes for a different amino acid
• EX of a point mutation

Question 14

What is a nonsense mutation?

Answer 14

• Changes a codon specifying an amino acid into a “stop” codon
• Results in a shortened protein product
• EX of a point mutation

Question 15

What are deletion/insertion mutations?

Answer 15

-Involving >1 nucleotide

Question 16

What is a frameshift mutation?

Answer 16

-Addition or deletion of bases that are not a multiple of 3 with disruption of the reading frame of the protein

Question 17

What are examples of deletion/insertion mutations?

Answer 17

• Frameshift mutation
• Codon deletions and insertions
• Expansion

Question 18

What are the classifications of inheritance patterns?

Answer 18

• Chromosomal abnormalities
• Mendelian inheritance (mongenic)
• Non-Mendelian inheritance (digenic)

Question 19

What are types of Non-Mendelian Inheritance?

Answer 19

• Mitochondrial
• Polygenic
• Modifier gene
• Multifactorial

Question 20

What are types of Mendelian Inheritance?

Answer 20

• Autosomal dominant
• Autosomal recessive
• Sex-linked (X- or Y-linked)

Question 21

What is aneuploidy?

Answer 21

• Abnormal # of chromosomes

- EX: sex chromosome aneuploidy, trisomy

Question 22

What are examples of chromosomal aberrations?

Answer 22

• Aneuploidy
• Translocations
• Deletions
• Contiguous gene syndromes
• Isochomosomes
• Inversions

Question 23

What is heterogeneity?

Answer 23

• Several different genes result in one phenotype

- EX: deafness, blood clotting disorders

Question 24

What is phenocopy?

Answer 24

• An environmental factor mimics a genetic condition and results in the same phenotype
• EX: hair loss from chemotherapy, mimics alopecia

Question 25

What is pleiotropy?

Answer 25

- One gene (or a pair of genes) causes multiple phenotypic effects in the body - EX: Marfan syndrome

Question 26

What is penetrance?

Answer 26

- The percentage of individuals who possess a dominant gene and express it - Incompletely penetrant (not every individual who has the genotype displays the phenotype)

Question 27

What is variable expressivity?

Answer 27

-A genotype producing a phenotype that varies among individuals

Question 28

Describe X-linked recessive inheritance.

Answer 28

- DFNX - M >>> F - No father-to-son transmission - All daughters of a male with the trait will be carriers - Carrier females: 50% chance to have sons with the trait, 50% chance to have carrier daughters - Trait may be transmitted trough a series of carrier females

Question 29

What is mitochondrial inheritance?

Answer 29

- Trait is passed through maternal line only - All offspring of a mother with the disorder will inherit the trait - No children of a father with the disorder will inherit the trait - M = F - Reduced penetrance, variable expressivity, and pleiotropy

Question 30

Describe the phenotype of nonsyndromic DFNA.

Answer 30

- Less severe than DFNB - Postlingual > prelingual - Sometimes hard to differentiate form environmental factors and aging - Genetically heterogeneous - SNHL - Progressive - ~70 DFNA loci - 35+ genes have been identified (some loci have more than one genes) - EX: DFNA6/14

Question 31

Describe the phenotype of nonsyndromic DFNB.

Answer 31

- ~56% of prelingual hereditary HL - Predominantly: prelingual SNHL, bilateral, severe-to-profound, stable, all frequencies - Tendency to partner with another deaf person - >100 loci mapped - EX: GJB2

Question 32

What are some genetic approaches to understanding auditory function?

Answer 32

- Gene regulation - Fluid homeostasis: gap junctions, ion channels, transporters - Junctional complex and tight junctions - Structural integrity - Synaptic transmission

Question 33

What are some examples of syndromic hereditary HL?

Answer 33

- Alport syndrome - CHARGE - Branchio-oto-renal (BOR) syndrome - Stickler syndrome - Treacher Collins

Question 34

What are the clinical features of Alport syndrome?

Answer 34

- Hematuria (blood in urine) - Nephritis with progressive renal failure - Eye abnormalities (i.e. cataracts) - Progressive SNHL with onset in late childhood to early adulthood

Question 35

What is the inheritance pattern for CHARGE?

Answer 35

- Heterozygous mutations | - Genes: CHD7, SEMA3E

Question 36

What is the inheritance pattern for Alport syndrome?

Answer 36

- X-linked - AR - AD - Genes: COL4A3, COL4A4, COL4A5

Question 37

What are the clinical features of branchio-oto-renal (BOR) syndrome?

Answer 37

- SNHL, CHL, or MHL - Branchial pits, cysts, and/or fistulae - Renal dysplasia or aplasia - Malformed pinnae - Ear pits and/or tags

Question 38

What is the inheritance pattern for BOR syndrome?

Answer 38

- AD | - Gene: EYA1

Question 39

What are the clinical features of Stickler syndrome Type I?

Answer 39

- SNHL, occasionally CHL - Progressive myopia - Midface hypoplasia - Retinal detachment - Mitral valve prolapse - Degenerative joint disease

Question 40

What is the inheritance pattern for Stickler syndrome?

Answer 40

- AD - Type I Gene: COL2A1 - Type II Gene: COL11A1 - Type III Gene: COL11A2

Question 41

What are the clinical features of Treacher Collins syndrome?

Answer 41

- Malar hypoplasia - Malformed auricles - CHL - Ear tags - Downward slanting palpebral fissures - Lower lid coloboma - Mandibular hypoplasia - Macrostomia

Question 42

What is the inheritance pattern for Treacher Collins syndrome?

Answer 42

- AD | - Gene: TCOF1

Question 43

What temporal bone lesions can be identified with CT scan.

Answer 43

- EVA - Mondini dysplasia - Lateral canal dysplasia (CDH7) - Calcification of cochlea (CMV, meningitis)