Genetics Flashcards
What is a genome?
- Complete set of genetic information, all the biologic information needed to build and maintain an organism
- Comprises all of the organism’s DNA
What is an exome?
- Protein coding portion of DNA
- ~1% of total genome
What is an intron?
- Non-coding sections of a gene
- Important biologic functions
What is a nucleotide?
- Nitrogen-containing base (A and G are purines; T and C are prymidines)
- Sugar
- Phosphate
- Nucleotide strand forms a spiral (double helix)
What is DNA transcription?
- mRNA takes coding to ribosomes where amino acids are formed
- Each tri-nucleotide sequence = codon
- 20 types of amino acids (each specified by codons)
What are amino acids?
- 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
What is a mutation?
-Change in a gene’s biochemical makeup, change at the DNA level
What is a mutagen?
- A substance that causes a mutation
- EX: raidation
What is a mutant?
-An allele that differs from the mild type (normal or most common) allele, altering the phenotype
What is a spontaneous mutation?
-A genetic change resulting from the mispairing of bases during replication
What is a mutational hot spot?
-Most likely to happen when the nearby DNA is repetitive or symmetrical
What is a point mutation?
-Involving a single nucleotide in the DNA molecule
What is a missense mutation?
- Change in a codon so that it codes for a different amino acid
- EX of a point mutation
What is a nonsense mutation?
- Changes a codon specifying an amino acid into a “stop” codon
- Results in a shortened protein product
- EX of a point mutation
What are deletion/insertion mutations?
-Involving >1 nucleotide
What is a frameshift mutation?
-Addition or deletion of bases that are not a multiple of 3 with disruption of the reading frame of the protein
What are examples of deletion/insertion mutations?
- Frameshift mutation
- Codon deletions and insertions
- Expansion
What are the classifications of inheritance patterns?
- Chromosomal abnormalities
- Mendelian inheritance (mongenic)
- Non-Mendelian inheritance (digenic)
What are types of Non-Mendelian Inheritance?
- Mitochondrial
- Polygenic
- Modifier gene
- Multifactorial
What are types of Mendelian Inheritance?
- Autosomal dominant
- Autosomal recessive
- Sex-linked (X- or Y-linked)
What is aneuploidy?
- Abnormal # of chromosomes
- EX: sex chromosome aneuploidy, trisomy
What are examples of chromosomal aberrations?
- Aneuploidy
- Translocations
- Deletions
- Contiguous gene syndromes
- Isochomosomes
- Inversions
What is heterogeneity?
- Several different genes result in one phenotype
- EX: deafness, blood clotting disorders
What is phenocopy?
- An environmental factor mimics a genetic condition and results in the same phenotype
- EX: hair loss from chemotherapy, mimics alopecia
What is pleiotropy?
- One gene (or a pair of genes) causes multiple phenotypic effects in the body
- EX: Marfan syndrome
What is penetrance?
- The percentage of individuals who possess a dominant gene and express it
- Incompletely penetrant (not every individual who has the genotype displays the phenotype)
What is variable expressivity?
-A genotype producing a phenotype that varies among individuals
Describe X-linked recessive inheritance.
- DFNX
- M»_space;> 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
What is mitochondrial inheritance?
- 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
Describe the phenotype of nonsyndromic DFNA.
- 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
Describe the phenotype of nonsyndromic DFNB.
- ~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
What are some genetic approaches to understanding auditory function?
- Gene regulation
- Fluid homeostasis: gap junctions, ion channels, transporters
- Junctional complex and tight junctions
- Structural integrity
- Synaptic transmission
What are some examples of syndromic hereditary HL?
- Alport syndrome
- CHARGE
- Branchio-oto-renal (BOR) syndrome
- Stickler syndrome
- Treacher Collins
What are the clinical features of Alport syndrome?
- Hematuria (blood in urine)
- Nephritis with progressive renal failure
- Eye abnormalities (i.e. cataracts)
- Progressive SNHL with onset in late childhood to early adulthood
What is the inheritance pattern for CHARGE?
- Heterozygous mutations
- Genes: CHD7, SEMA3E
What is the inheritance pattern for Alport syndrome?
- X-linked
- AR
- AD
- Genes: COL4A3, COL4A4, COL4A5
What are the clinical features of branchio-oto-renal (BOR) syndrome?
- SNHL, CHL, or MHL
- Branchial pits, cysts, and/or fistulae
- Renal dysplasia or aplasia
- Malformed pinnae
- Ear pits and/or tags
What is the inheritance pattern for BOR syndrome?
- AD
- Gene: EYA1
What are the clinical features of Stickler syndrome Type I?
- SNHL, occasionally CHL
- Progressive myopia
- Midface hypoplasia
- Retinal detachment
- Mitral valve prolapse
- Degenerative joint disease
What is the inheritance pattern for Stickler syndrome?
- AD
- Type I Gene: COL2A1
- Type II Gene: COL11A1
- Type III Gene: COL11A2
What are the clinical features of Treacher Collins syndrome?
- Malar hypoplasia
- Malformed auricles
- CHL
- Ear tags
- Downward slanting palpebral fissures
- Lower lid coloboma
- Mandibular hypoplasia
- Macrostomia
What is the inheritance pattern for Treacher Collins syndrome?
- AD
- Gene: TCOF1
What temporal bone lesions can be identified with CT scan.
- EVA
- Mondini dysplasia
- Lateral canal dysplasia (CDH7)
- Calcification of cochlea (CMV, meningitis)
