Principles Of Genetic Inheritance Flashcards
Banding and nomenclature:
What does 17q11.2 mean
17th chromosome Q = longer arm 1 = closest band to the centromere 1 = band staining technique .2 = specific portion of band 1
When is a karyotype made
During metaphase of the M phase
After replication
Lionizations (X-inactivation)
The inactivation of one of the X chromosomes in females; performed randomly
Mosaicism
A condition in which cells from a patient have different genotypes an karytopes
Mosaicism and Turner’s syndrome
Some cells will have 46XX (normal) and some will have 45XO
Around 30% of turner’s syndrome cases demonstrate mosaicism
Mosaicism and Down’s syndrome
Some cells are 46XX (normal) and some are 47XX+21
Mosaicism and Klinefelter Syndrome
Some cells are 46XY (normal) and some are 47XXY
How do stem cells divide
They undergo mitosis, but divide asymmetrically, resulting in one stem cell and one daughter cell
Homologous recombiantion (crossing over)
Produces new combinations of genes; part of the maternal chromosome switches with its counterpart in the paternal chromosome, resulting in a recombination of genes
Two ways in which meiosis creates genetic diversity
- Random segregation of homologs
2. Cross-over exchange (homologous recombination)
Euploid
Cells with normal number of chromosomes
- haploid gametes and diploid somatic cells
Polyploidy
Presence of a complete set of extra chromosomes in a cell
- often seen in plants
Aneuploid
Cells with a missing or additional individual chromosomes
- monosomy and trisomy
Symptoms of Turner Syndrome
45, XO karyotype
Female
- short
- ovarian hypofunction/premature ovarian failure
- need hormone therapy for puberty
- infertility
- webbed neck (in 30% of cases)
- low hairline on neck
- cardiovascular defects
- normal intelligence ***
Symptoms of Klinefelter syndrome
47XXY
Male
- cognitive, social, behavioral, learning difficulties
- primary hypogonadism (low T)
- small/undescended testes
- tall
- infertility
- gynecomastia (male breasts)
Patients can also not show symptoms
Reciprocal translocation
An exchange of material between nonhomologous chromosomes
Robertsonian translocation
When the long arms of two acrocentric chromosomes are combined and the short arm is lost (typically)
Patau Syndrome
47XX+13
Severe developmental abnormalities
Most perinatal death within 1 week
Edwards Syndrome
47XX+18
Abnormal development
Most perinatal death within 1 year
Genomic Imprinting
Essentially gene silencing through methylation of 5’ region of the gene
Causes chromatin condensation
At least 100 human genes are known to be imprinted
- clustered together
~ 30 genes that are paternally imprinted and maternally expressed
~ 70 genes that are maternally imprinted and paternally expressed
What happens to imprints during meiosis in germ cells
They are erased and new ones are set
Prader-Willi syndrome
Deletion of PWS region/AS gene on paternal chromosome 15
- short
- hypotonia (weak muscle tone)
- small hands and feet
- obesity
- mild/moderate intellectual disability
Angelman Syndrome
Caused by a deletion in PWS region/AS gene on the maternal chromosome 15
- severe intellectual disabilities
- seizures
- ataxic gait
Uniparental disomy
When two chromosomes are inherited from the same parent, instead of one being inherited from the father and one from the mother
Caused by nondisjunction in mother or father, which will cause 1/3 of gametes to have two chromosomes of one parent and none of the other
Can cause Prader Willi and Angelman
Law of segregation in Mendelian genetics
Allele pairs separate during gamete formation and randomly unite during fertilization
Law of independent assortment in Mendelian genetics
Individual hereditary factors assort independently during gamete formation
Does cystic fibrosis stem from multiple genotypes or multiple phenotypes
Distinct genotypes, single phenotype
Do patients with PKU have multiple genotypes or multiple phenotypes
Same genotype for all patients, multiple phenotypes (pleiotropy)
Pleiotropy
When individuals have the same genotype but multiple possible phenotypes
Proband (propositus)
First diagnosed person in a pedigree
What kind of inheritance causes postaxial polydactyly
Autosomal dominant
Albinism is caused by what kind of inheritance
Autosomal recessive
Duchesse muscular dystrophy is caused by what kind of inheritance
X-linked recessive
Hypophophatemia is caused by what kind of inheritance
- also what is it
X-linked dominant
Low phosphorus in the blood due to defective reabsorption of phosphate in kidney
Deficient absorption of calcium in intensities casting softening of bone (rickets)
Penetrance
The degree to which a gene manifests itself
Retinoblastoma is caused by what kind of gene expression and gene inheritance
Reduced penetrance
Phenotype occurs in 90% of individuals inheriting gene defect, so 90% penetrance
Autosomal dominant inheritance
Neurofibromatosis is caused by what kind of gene expression
Variable expressivity
Patients have pigmented areas the color of coffee with cream (cafe au lait spots)
Patients also developed tumor-like growths called neurofibromas
Variable expressivity
When there is a range of phenotypes that vary between individuals with a specific genotype
- Neurofibromatosis
Locus heterogeneity
A single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
Ex: osteogenesis imperfecta
- can be caused by mutation at chromosome 7 or 17
Osteogenesis imperfecta is caused by what genetic defect
Locus heterogeneity
Can be caused by mutations in collagen genes at two different loci (chromosome 7 or chromosome 17)
Mutations at 7 or 17 will both cause the disease
How to calculate the probability of ~either~ one outcome or another
Addition rule
Sum of the two probabilities
How to calculate the probability of ~both~ outcomes occurring
Multiplication rule
Multiply the probabilities together
How to calculate genotype frequency
of that genotype/ total # of genotypes in that study
How to calculate allele frequency
of individual alleles/ total # of alleles in the study
Total # of alleles in the study is the # of people x2 (2 alleles per person)
Cystic fibrosis is caused by what kind of inheritance
Autosomal recessive
Autosomal dominant inheritance characteristics
- only one parent is affected
- vertical transmission of disease phenotype
- no skipped generations
- equal male and females affected
- father —> son transmission
- recurrent risk: 50%
Autosomal recessive inheritance characteristics
- parents are normal
- clustering of disease phenotype among siblings
- disease not usually seen among parents or other ancestors
- equal number of males and females affected
- consanguinity ~may~ be present
- recurrent rate: 25%
consanguineous mating
Incestuous mating; second cousin or closer
More likely to produce offspring affected by rare autosomal recessive disorders
Each person carries 1-5 recessive mutations lethal to offspring if matched with another copy of the mutation
Mitochondrial DNA (mtDNA)
- several copies of 16,569 double stranded circular mtDNA per mitochondria
- encodes rRNA, tRNA, and 13 polypeptides
- transcription takes place in mitochondria, not nucleus
- no introns
***inherited exclusively through maternal line
Why is the mutation rate higher in mitochondrial DNA
Relative lack of DNA repair mechanisms
Damage from free oxygen radicals released during oxidative phosphorylation
Mitochondrial inheritance
All children get mitochondrial DNA from their mother; if the mother has a disease associated with mtDNA, every child will have it
Men will have the mtDNA but do not pass it to their offspring if their wife is normal
Leber’s hereditary optic neuropathy (LHON)
Mitochondrial disorder
Degeneration of retinal ganglion cells
Acute or subacute loss of central vision
- typically in early teens or 20s
Mitochondrial encephalopmyopathy, lactic acidosis, and stroke-like episodes (MELAS)
Mitochondrial disorder
Affects many body systems, particularly brain and nervous system, and muscles
Stroke and dementia
Lactic acidosis
Polygenic traits
Traits caused by combined effects of multiple genes
Multifactorial traits
When environmental factors cause variation in traits
Pyloric stenosis
- what kind of inheritance causes it
- men vs women
Multifactorial inheritance
5x more common in males than females
Why? Males need less risk genes to show disease
Women transmit the disease more than men, however
Multifactorial inheritance
Caused by the simultaneous influence of multiple genetic and environmental factors
Metacentric chromosome
Centromere is at the mid region, short and long arms are more equal
Submetacentric chromosome
The centromere is off from the center of chromosome, but both haves matter
Acrocentric chromosome
Centromere is very pushed off to one side and there is very little info on the short side of the chromosome
What happens to epicenetic imprints in somatic cells
They remain through the lifespan of the individual
Punnet Square and pedigree for autosomal dominant inheritance
Aa x aa; 50% of offspring expected to have disease
One parent is affected; females can give disease to males and males can give the disease to females; trait expected in 50% offspring
Punnet square and pedigree for autosomal recessive inheritance
Need two copies of the gene to influence phenotype
Aa x Aa
(Carrier female with carrier male)
Both parents are normal; recurrent with heterozygous parents is 25%; affects males and females equally
Which inheritance is more common with consanguinity (first cousins mating)
Autosomal recessive inheritance
How X-linked recessive inheritance is passed on to daughters and sons
Affected males will pass the disease on to 100% of their daughters
Affected females will pass the disease on to 50% of their daughters and 50% of their sons
How is X-linked dominant passed down to sons and daughters
Affected males will pass disease on to 100% of daughters
Affected females will pass disease to 50% of daughters and 50% of sons
Mitochondrial inheritance pedigree
DNA is passed through the mother
The original mother will be affected, all of her children will be affected, and all of her grandchildren of her affected daughters will be affected
Threshold of liability
The threshold that must be crossed before the disease is expressed; concept used in multifactorial diseases that are either present or absent
Below the threshold, the person appears normal
Above the threshold, the person is affected by the disease
