genetics Flashcards
what is a gene?
basic unit of inheritance
what is a locus?
-physical location of a gene on a chromosome
what is an allele?
-alternative forms of a gene at a given locus
what is the difference between homozygous and heterozygoud?
homo-identical allels at a single locus
hetero- different alleles at a single locus
dominant and recessive refer to what?
-phenotypic expression, not the gene itself
what kind of condition is seen in homo and hetero?
dominant
somatic cells
- all cells in body except gametes
- always diploid
gametes
- sperm or egg cells
- always haploid
what are single gene disorders?
- produces by the effect of a single gene (or gene pair)
- usually transmitted in simple patterns as autosomal dominant, recessive, or X-linked
- also called mendelian disorders
what are chromsomal abnormalities?
-deviation from the normal chromosome number or structure
what are multifactorial traits?
-combined effects of multiple genetic and non-geneic influences
congenitial?
- disease or condition present at birth
- can be hereditary or aquired
how many mutatant alleles are needed for an autosomal dominant disease to be expressed?
-one
autosomal dominant often involves what kind of proteins?
non-catalytic
Autosomal dominant: what sex can be effected? male to male transmission?
- either sex can be effected
- yes male to male
what is recurrence risk?
- probability that offspring of a couple will have the genetic disease
- each reproductive event is statistically INDEPENDENT of all other previous events
how many mutant alleles are needed for an autosomal recessive disease to be expressed?
two
a person effected by autosomal recessive disease usually has what kind of parents?
- unaffected parents
- USUALLY
autosomal recessive: sex? male to male?
- either sex can be affected
- NO MALE TO MALE
both parents of a child with autosomal recessive disease are at minimum…
obligate carriers
what kind of proteins are involved with autosomal recessive>
catalytic
what is the recurrence risk probability for autosomal dom? recessive?
dom: 50% usually
rec: 25% usually
examples of autosomal dom?
- huntington
- myotonic dystrophy
- marfan
examples of autosomal reessive?
- sickle cell
- cystic fibrosis
- PKU
X-linked always means what
X-linked recessive
-x linked dominant is so rare with no high yeild disease that we dont care
who is normally effected by X-linked recessive? is there male to male transmission?
males
-no male to male transmission of mutant allele
affected kid of x-linked usually has what kind of mom
-unaffected carrier
examples of X-linked recessie?
- duchenne and Becker muscular dystrophy
- lesch nyhan
- G6P dehydroenase deficiency
- hemophilia A and B
mitochondrial inheritance
- during fertilization, sperm do not pass their mitochondria to the egg cell
- mitochondrial disease are inferited EXCLUSIVELY from mom
what is so special about mitochondria
- only organelle that contain their own DNA
- mDNA
how much of the offspring is affected when a mom has a mitochondrial disease?
all of them!
Mitochondrial disease: sex affected? male to male transmission?
- both sexes can be affected
- no male to male duh
examples of mitochondrial inheritance?
- leber hereditary optic neurophathy
- blindness
- optic atrophy
does mitochondrial inheritance follow mendalian genetics?
- nope
- no recurrace risk to calculate
if looking at a pedigree, what is a sure sign that it is mitochondrial inheritance?
-transmission only through affected moms and never through affected dads
what are teh two general types of single gene disorders?
- loss of function
- gain of function
loss of function mutations can have defects in what proteins
- structural
- regulatory
what is a gain of function mutation?
- normal proteins with toxic properties
- huntingtons
neurofibromatosis Type 1: what kind of inheritance? what is the gene defect? what is the incidence rate? what is the noteable genetic concept?
- autosomal dominant
- mutation in a cell cycle regulatory protein (loss of function)
- 1 in 3000
- variable expression: different expression even within the same family
what is a clinical sign of neurofibromatosis Type 1, even through variation?
-lisch nodules in eye
Marfan syndrome: what kind of inheritance? what is the gene defect? good example of what genetic principle?
- autosomal dominant
- mutation in fibrillin gene
- pleiotropy
what is pleiotropy?
when a single mutation affects multiple organ systems
what occular abormalities are seen with marfan syndrome?
-myopia and detached lens
what are the systemic problems seen with marfan sysndrome?
- hypermobile joints
- thin long limbs
- cardiovasvular disease
Thalassemias: what kind of inheritance? what is the gene defect? what part of the world is it commonly seen in?
- autosomal recessive
- imbalance in globin chain synthesis
- around the mediterranean sea
what is the most common single gene disorder?
thalassemias
what are the two types of thalassemias?
- alpha: insufficient synthesis of the alpha chain, beta chain accumulates
- beta: insufficient synthesis of the beta chain, alpha chain accumulates
thalassemias causes what and results in what?
- causes premature death of cells destined to become red blood cells
- results in hemolytic anemia
males are said to be _____________ for genes on the X chromosome
hemizygous
Hemophilia A and B: what kind of genetic inheritance? what is the gene defect? what is the severity of the disease related to?
- X-linked
- absence/defect of a clotting factor
- lost of mutation types, so severity is related to the mutation type
what is the most frequent cause of death for people with hemophilia A and B?
- AIDS
- treatment for the disease is blood transfussion and blood cannot be cleaned before, so aids can be transmitted
why do we have X-inactivation? what is it also called?
- females would have two fold excess of X chromosome so exression is down regulated
- also called lyonization
the inactive X chromosome can be observed as….
-condensed barr body in nuclei of interphase cells
X inactivation is associated with what kind of DNA?
-highly methylated
Characteristics of X inactivation
- occurs early in development of female embryos
- occurs randomly (could be X from mom or dad)
- is is FIXED( once inactivated, all cells descended from that one are also inactivated)
- X inactivation is incomplete (some genes on inactivated one remain available for transcription)
the fact that X inactivation is incomplete explains what?
- why some female heterozyotes with one mutant X chromosome can still show symptoms of a X-linked recessive disease
- why symptoms can be less severe and variable in some cases
what is delayed age of onset
- rare cases of single gene disorders that do not manifest until later in life (30s and 40s) IN FIRST SYMPTOMATIC GENERATION. EARLY ON IN PEDIGREE
- huntington and myotonic dystrophy
- as it is inherited, symptoms will show up earlier
what is locus heterogeneity? example?
- when the same disease phenotype can be caused by mutations in difference loci
- inheritance pattern is different
- Ehlers-danlos syndrome
mutations in EDS autosomal dominant? autosomal recessive? X linked?
Autosomal dominant: mutation in collagen genes
Autosomal recessive: mutation in lysyl hydroxylase
X-linked: mutation in copper binding protein (needed for cross linking of collagen fibers)
new mutations?
- all genetic disease start with a new mutation
- in cases with high mortality or low fertility (very rare diseases)
- mainly dominant or X-linked where phenotype is seen immediately in the pedigree
- often weeded out
what is anticipation? what kind of diseases is it normall associated with?
- refers to diseases where the most recent generations of affected individuals show 1. EARLIER ONSET 2. MORE SEVERE SYMPTOMS than previous generations
- associated with diseases caused by trinucleotide repeat expansions
the severity of diseases with anticipation are directly correlated to….
-the length of the segment containing the trinucleotide repeats
even though something is considered an adult disease, it can appear in early childhood, why?
- anticipation would make symptoms show up earlier and more severe
- each generation it would show up earlier and earlier
what are he assumptions that have to be there for hardy-weinberg?
- population is large
- individuals mate at random
- constant and predictable relationship between genotype frequencies and gene frequencies
if there are only two alleles, what must the gene frequency add up to for hardy weinburg?
1
hardy weinburg helps you figure out what?
- figure out genotype frequencies if we know gene frequencies
- vice versa
- AUTOSOMAL RECESSIVE INHERITANCE ONLY
what is the primary source of all new genetic variation in populations?
- mutation
- mutation rates do not differ much from population to population
natural selection
-influences gene frequencies by selecting for genes that promote survival or fertility -FITNESS
what kind of diseases are more exposed to gene selection?
dominant
-cannot remain hidden like heterozygotes
Heterozygote advantage for sickle cell? thalassemia? cystic fibrosis?
- Sickle Cell: plasmodium parasite doesnt survive very successfully so heterozygotes usually escape the worst infection of malaria
- Thalassemia: some protection against malaria
- cystic fibrosis: protection against typhoid fever
when does genetic drift occur??
- populations with finite population size
- rapid in small populations
what is genetic drift/founder effect?
-rare alleles are present in higher abundance in a small, isolated population that goes on to colonize an area
what is Ellis Van creveld disease? example of what?
- rare autosomal recessive
- defective EVC gene
- multiple digits, dwarfism
- amish
- founder effect/genetic drift
what is gene flow?
- exchange of genes among populations
- seen more frequent now because parts of the world are not as isolated and the heart wants what the heart wants
