Flashcards in Genetics and Genomics Deck (66):
What is a haplotype?
=an individuals set of alleles at a locus or cluster or loci on a chromosome
What are single gene disorders?
-these disorders are determined primarily by the alleles at a SINGLE locus
-recurrence risk describes the likelihood of passing on the gene
Mendelian Genetics... what is it concerned with?
-monogenetic traits aka single gene traits
is one gene locus is independently transmitted from a gene on a different locus
Autosomal dominant disease
seen in every generation
-structural genes are often seen in this inheritance pattern
-no skipping generations **unless new mutation!**
-probability to inherit=50%
their limbs (humerus and femur) are short but their tib/fib and radius/ulna are normal length
What is the danger with 2 people who have an AD disease mating?
-they have more problems in those who will become homozygotes much more severe issues
-often seen in metabolic disorders
-this is sometimes seen in those who are relatives who mate CONSANGUINITY
-those that are heterozygotes may have reduced enzyme activity and then combine to make no activity
-probability to inherit from heterozygote parents 25%
What is hurler syndrome?
-similar to hunter
-mutation to CTFR gene
-Cl transporter mutation
-pleiotropic: effects more than one organ
Remember that dominant and recessive refer to ___ not ___
traits not genes!
Sex linked inheritance
X linked dominant
X linked recessive
x chromosome: larger so more mutations
-common in men
y linked: much smaller contains less genes
X linked recessive
M > F--bc males usually only ones affected
-SONS of heterozygote mothers have 50% chance of being affected
X linked dominant
M and F can be affected
-all female offspring of affected father will be affected
only father to son transmission
-only given from mother
-all offspring of affected females show signs of disease
-not all mitochondria congregate in specific organs... so they effect organs different =heteroplasmy
-this can complicate the "normal" pattern of inheritance
-the gene transmitted undergoes a mutation from the normal allele
Achondroplasia and risks and what they have!
-most cases are due to new mutations
-only 1/8 are transmitted from dwarf parents
-distinguish this by taking a family hx
remember they are: Rhizomelic---> refers to either a disproportion of the length of the proximal limb, such as the shortened limbs of achondroplasia, or some other disorder of the hip or shoulder.
What is gremlin mosaicism?
-when 2 or more offspring present with an AD disease with no familial hx
-this is when all parts of the germline cells are affected by the same mutation
-mutation occurs during the parents embryonic development of the germ cells
Age Dependent Penetrance
aka delayed age onset
-ex. of this is BRCA gene
-this is when the disease does not present until AFTER patients reach reproductive age or adulthood
-this can cause a difficulty in detecting the mode of inheritance
polycystic kidney disease
-this is when those that have the genotype fail to express the appropriate phenotype although they pass it to the next generation
penetrance is the general idea that a phenotype expression is dependent upon the predisposing genotype
a trait in which the same genotype can produce phenotypes of varying severity or expression
-severity is what varies
-a parent with midl expression may pass on the disease
What are some causes for variable expression?
1. environmental factors
2. modifier genes
3. allelic heterogeneity
What is pleiotropy?
-genes that affect multiple aspects of physio or anatomy
ex. sickle cell
-mutation to fibrillar
ex. of pleiotropy
=single disease phenotype caused by mutations at different loci in different families
a risk of this is testing for the wrong mutation
Genomic Imprinting... ex. of this
=process by which genetic material is expressed differently when inherited from the mother than when inherited from the father
ex. prader will an anglemans
Prader willi is inherited from the PATERNAL side
Anglemans is MATERNAL (heavy retardation)
=progressivle earlier onset and increased severity of certain diseases in successive generations of a family
ex. myotonic dystrophy
Population genetics: what factors determines it?
the branch of genetics dealing with genetic variation and genetic evolution of population
-it looks at how these frequencies change or are maintained in different populations
a. genetic factors
b. environmental and societal factors
What is the multiplication rule?
probability that BOTH event 1 and 2 will occur together
multiply probabilities together
What is the addition rule?
probability that EITHER event 1 or 2 will occur together
add the probabilities together
states that population frequencies will stay at a constant from generation to generation
*calculates genotype frequencies
p^2 +2pq + q^2=1
what are the assumptions for hardy weinberg to be true? 4
1. large population
2. no mutation
3. no selection
4. no migration
when is hardy weinberg used in the clinical setting?
often used for autosomal recessive conditions
what is the 2/3 rule?
2/3 for heterozygotes who are carriers and do not have disease. 1/4 chance for child who does not have the disease and multiple these by the population frequency
What are some causes in population change frequencies?
1. natural selection
2. genetic drift
3. founder effect
4. gene flow
natural selection... ex. of some diseases
-sickle cell: protects from malaria
-CF: protects against diarrhea
leiden V: entourage coagulation
What are some examples of the founder effect?
-the founder effect is a large shift in frequencies in a small population containing little genetic variation
-often subsets of populations
b. small towns
c. ashkenazi jews
Why is knowing the ethnic population of your patient important for genetic testing?
-if you know the ethnic population you can order more specific genetic testing
-this can ultimately save cost
What is cytogenetics?
=the study of chromosomes and their abnormalities
-uses cytology and genetics
What is a karyotype? What criteria are they numbered by?
-chromosomes are extracted from nucleus, stained, and matched according to
b. banding patterns
c. location of centromere
nomenclature for chromosomes
p=petitie small arm
metacentric: equal on each side of centromere
submetacentric: longer on once side
acrocentric: very small p arm
What is the problem with acrocentric chromosomes?
they often can have robertsonian translocations
What is euploid?
a multiple of a haploid number (N=23)
What is aneuploid?
trisomy or monosomy
=extra or missing chromosomes
-it is the state of not having euploidy
**most common cause is nondisjunction**
When does nondisjunction occur?
it can occur during meiosis 1 or 2.
-Often occurs during meiosis 1 in female gametes
-it can occur in men but much later in life at about ~60 years old
What is polyploidy?
=more than 2 sets of homologous chromosomes
2 sperm--1 egg
1 sperm--diploid egg
Down syndrome... what is its MAIN cause?
47 chromosomes (21)
-early onset alzheimers
main cause: maternal meiosis I
lots in prison population?
-could also have mosaic turners which are fertile therefore it is important to know where its full turners or not
-this is the SINGLE MOST COMMON ABNORMALITY IN ABORTIONS
-overlap of middle and index fingers
-only 5% survive to 1 year
-From maternal side
-absence of speech
Whats the difference between genetics and genomics?
genetics: study of traits
genomics: is the study of genes
Inactivating changes in genes
-these are more common that activating changes
-mutations which reduce expression
-reduce activity of protein
-can alter splicing balance
What are reasons for gaps in the genome?
1. chromosomes are not continuous
2. some sequences are hard to read high GC
3. some sequence is hard to align--repeats
human genome is the ARTIFICIAL reconstruction of chromatin
What is some evidence for a genetic contribution to a disease?
1. congenital disorders
2. family hx
3. cross cultural
6. identical twins separated at birth *ideal*
7. expression analysis
what is missing heritability?
-we know its heritable but we do not know the gene for it
Lamina A mutations
C--> T conversion
-mutation is absent in both parents
-usually acquired from a gremlin mutation
-it is what causes progeria
What is the difference between family Hx and Genetic status?
They are often used interchangeably but they are 2 different things
Family hx: stress, diet, exercise, infections, drugs/alcohol, exposure level to various things
genetic statusL shuffling, mutation to germ line, donor egg, adoption
where do they overlap? SNPs, most disease risks
What are PROBLEMS with family hx?
-not recorded in a usable format
-mistakes in recalling cause of death
-many know little about health hx due to secrecy, and low privacy rates
-adoption or donor eggs
-health records die with people
What are some advantages to multi-generational pedigree analysis?
-families have low genetic noise (they are very similar)
-example ashkenazi jews
1. gene is perfectly associated with disease
*high penetrance- typical of monogenic
2. gene is poorly associated with disease
*low penetrance- typical of multi genic diseases
3. gene is strongly associated with disease but at variable levels
*high penetrant but variable EXPRESSIVITY