(L13) Principles of Genetic Inheritance Flashcards
What does the term proband mean?
L9 S9
The person from whom a pedigree is initiated
What are characteristics of an autosomal recessive trait genotypically and on a pedigree?
L13 S10
Genotype:
-requires two copies of the gene for phenotype
Pedigree:
-present equal in both sexes -can skips generations
What are characteristics of an autosomal dominant trait genotypically and on a pedigree?
L13 S5-7
Genotype:
-Only requires 1 copy of the gene for phenotype
Pedigree:
- present equal in both sexes
- affected people have an affected parent (does not skip generations)
- unaffected people do no transmit the trait (does not skip generations)
What are characteristics of an X-linked recessive trait genotypically and on a pedigree?
L13 S11
Genotype:
-one copy of gene on X chromosome for males; two copies for females for phenotype
Phedigree:
- appears more frequently in males
- males do not pass the trait on to sons but can pass it onto daughters
- all daughters of affected males will at least be carriers
What are characteristics of an X-linked dominant trait genotypically and on a pedigree?
L13 S19
Genotype:
-requires only one gene in both males and females
Pedigree:
- does not skip generations
- all daughter of affected males are affected
- half the sons of affected, heterozygous females are affected
- carriers do not exist
What are characteristics of a Y-linked trait genotypically and on a pedigree?
Genotype:
-males with allele are affected
Pedigree:
- only appears in males
- all sons of affected males are affected
How could you distinguish between an autosomal recessive trait with higher penetrance in males and an X-linked recessive trait?
A father could pass down an autosomal recessive trait to his son but not an X-linked recessive trait.
Differentiate between monozygotic twins and dizygotic twins.
Monozygotic:
- “identical” twins
- share the same DNA sequence
Dizygotic:
- “fraternal” twins
- as similar DNA as normal siblings
Define concordiant trait and concordance.
Concordiant trait:
-trait shared by both members of a twin pair
Concordance:
-percentage of twin pairs that are concordant for a trait
What are characteristics of an mitochondrial inherited trait genotypically and on a pedigree?
L13 S12-14
Genotype:
-several mitochondria are present in each cell and a certain threshold of disease mitochondria are required for phenotype
Pedigree:
-only passed down my mothers
What is LHON?
What is its mechanism?
What are the symtpoms?
L13 S15
Leber’s hereditary optic neuropathy
Degeneration of retinal ganlion cells due to NADH dehydrogenase mutation resulting in not enough energy.
Results in loss of central vision
What is MERRF?
What is its mechanism?
What are the symtpoms?
L13 S16
Myoclonic epilepsy and ragged red fibers
Caused by a mutation in tRNA for lysine which disrupts cytochrome-c oxidase
Symptoms include ataxia and seizures
MELAS
What are the symtpoms?
L13 S17
Mitochondrial encehpalomyopathy, lactic acidosis, and stroke-like episodes
Symptoms typically neurologic or muscular
What do the terms euploid, polyploid, and aneuploid mean?
L13 S21
Euploid:
-normal number of chromosomes
Polyploid:
-complete extra set of chromosomes
Aneuploid:
-missing or additional individual chromosomes
What is the result of nondisjunction?
L13 S22
Trisomy and monosomy
What is genomic imprinting?
L13 S23;25-26
Pattern of DNA methylation and histone modificaiton that results in selective gene silencing without alteration of DNA sequence.
Imprinting occurs gametogenesis and is unique to the sex of the parent. During division of somatic cells, imprinting patterns are maintained.
What is uniparental disomy and how does it occur?
When can it cause issues?
L13 S23-24
Condition in which an individual has two copies of a chromosome from a single parent and no copy from the other parent.
Occurs due to errors in mitosis or early fetal development.
Typically this is not a problem unless a gene that is affected is imprinted and therefore there is no functional copy of that gene.
What are the main types of chromosomal mutations?
L13 S27
Inversion:
-segment of DNA is in reverse order of normal
Deletion
Duplicaiton
Translocation:
-exchange of DNA on two seperate chormosomes
What is the karyotype of Turner syndrome and what is the sex of the individual?
What are the key symptoms?
L13 S30
Females with a karyotype of 45, XO
Major symptoms:
- short stature
- webbed neck
- no puperty; no secondary sex traits, ammenorrhea
What are Prader-Willi and Angelman syndromes and what are the symptoms?
What is special about them?
L13 S31
Both result from deletion a portion of chromosome 15. The region contains two imprinted genes, one paternal and one maternal. Which parents chromosome the deletion occured on results in one of the two syndromes.
Prader-Willi syndrome:
- deletion of region on paternal chromosome
- uncontrolled eating, intellectual disability, short stature
Angelman syndrome:
- deletion of region on maternal chromosome
- severe intellecutal disability, seizures, ataxia
What is the karyotype of Klinefelter syndrome and what is the sex of the individual?
What are the key symptoms?
L13 S32
Males with karyotype of 47, XXnY (at least one extra X chromosome)
Major symptoms:
- hypogonadism and small testes
- parital female secondary sex characteristics
- tall stature
- cognitive, behavioral, and learning difficulties
What is trisomy 21 and what are the main characteristics?
L13 S33-34
Downs syndrome
Characteristics:
- cognitive impairment
- flattened nose and face, upward slanting eyes
- caridac defects
- duodenal atresia
What is trisomy 18 and what are the characteristics?
L13 S35
Edwards syndrome
95% die in utero, few survive to 1 year
Characteristics:
- microencephaly with prominent occiput
- malformed ears
- overlapped fingers
- rocker bottom feet
What is trisomy 13 and what are the characteristics?
L13 S36
Patau syndrome
Most die in utero, few survive past 1 week
Characteristics:
- cleft lip/palate
- close spaced or absent eyes
- clenched, polydactyl hands
- microcephaly
What is variable expressivity?
L13 S39
Range of phenotypes possible from individuals with the same genotypes
What is Marfan syndrome?
L13 S40
Defect in fibrilin resulting in variable effects in connective tissue.
What is locus heterogeneity?
L13 S41
Single disorder, trait, or pattern of trait caused by a mutation of at least one of a group of genes.
eg. Osteogenesis imperfecta
What is penetrance?
L13 S38
The rate at which a phenotype is actually present in people with the associated genotype.
When are probabilities added or multiplied?
L13 S44
Added:
-when considering the probability of “one or the other” occuring
Multiplication:
-when considering the probability of multiple outcomes occurring together; “this and that”
What is the difference between allele frequency and genotype frequency?
L13 S46
Allele frequency:
- frequency of alleles present in a population
- ie. A:a
- remember all individuals have 2 alleles
- does not indicate frequency of genotypes
Genotype frequency:
-frequency of genotypes in a population -ie. AA:Aa:aa
What is the Hardy-Weinberg principle and what is it used for?
L13 S48
p^2+2pq+q^2
Specifies the relationship between gene/allele frequency (p:q) to genotype frequency
What does the term consanguineous mean and what are the implications?
L13 S52
Mating occuring between closely retaliated individuals.
Mortality rates of offspring are increase (9% increase between first cousins)
What is heteroplasmy?
L13 S18
Panini pg. 330
Becuase there are multiple mitochondira per cell, there are also multiple copies of mitochondiral DNA.
Diseases involving mitochondrial DNA do not follow typical dominant and recessive phenotypes and instead diseased mitochondira must exceed a certain threshold of prevalence for symptoms to occur.
Necessary threshold often gets lower with age so somebody who may not have had symptoms at a younger age could develop them later in life.
