Genetics Exam II

the probability of one or more mutually exclusive events occurring is equal to the sum of their individual probabilities (odds of inheriting one trait)

sum rule

the probability of two or more independent events occurring simultaneously, is equal to the product of their individual probabilities (odds of inheriting different combinations of traits)

product law of probabilities

ideal ratio of phenotypes among offspring (progeny) that results when two dihybrids mate

mendels 9:3:3:1 dihybrid ratio

three factor cross

trihybrid cross

hypothesis that there is no real difference between measured values and predicted values

null hypothesis

probability that your results deviated from the expected (hypothesized) results by chances alone.

probability value (p)

test to determine if there is a significant difference between measured values and predicted values

chi squared test

the number of categories (n) - 1

df

individual who first brought attention to the family

proband

not a sex chromosome

autosomal

parents are related

consanguineous

twins derived from the same fertilized egg

identical (monozygotic) twins

twins derived from different fertilized eggs

fraternal (dizygotic) twins

a fatal genetic disease caused by loss of function mutation in HexA genes - gangliosides build up in the lysosomes and kill neurons

tay-sachs disease

caused by mutations in both alleles of the gene for phenylalanine hydroxylase (PAH), found on chromosome 12

Phenylketonuria (PKU)

non functional LDL-receptors prevent uptake of cholesterol into cells so that cholesterol increases in blood

familial hypercholesterolemia

the allele that occurs most frequently in a population

wild-type allele (wt)

a mutant allele that produces no function gene product. Usually inherited as a recessive trait.

null allele

a mutation with no perceived immediate phenotypic effect

neutral mutation

a mutation that creates alleles encoding proteins with reduced or no function.

loss-of-function (LOF)

chloride ion channel that prevents mucous buildup in bronchi. mutations in CTFR result in this; a fatal lung disorder

cystic fibrosis transmembrane conductance regulator (CFTR)

a mutation in which the gene product takes on a new function and produces a phenotype different from that of other alleles

gain of function mutation (GOF)

sodium channel in which a GOF mutation increases the sodium pumped into the neuron, causing epileptic seizures

SCN8A (sodium voltage-gated channel alpha subunit 8)

apolopoprotein that helps carry cholesterol in the bloodstream.

• most abundant apoloprprotein in the brain, mainly expressed by astrocytes & microglia to regulate cholesterol metabolism

• exists in several different forms (alleles) in the population

apolipoprotein E (APOE)

most common APOE isoform

• neutral for the development of Alzheimers Disease

WT = APOE3

allele with mutation that increases binding to B amyloid. (increase plaques)

• creates binding preference (VLDL ~bad cholesterol) over high density lipoprotein (HDL ~good cholesterol)

• ~15-25% of the population; 4x risk to develop AD earlier & greatest risk factor gene for alzheimer’s disease

gain of function = APOE4

allele that has deficient receptor binding (lowers cholesterol uptake by cells)

• rare in population

• may confer some protection against Alzheimer’s disease & atherosclerosis

• prevents lysosome cholesterol ester, tau & lipofuscin accumulation in microglia

Loss of function = APOE2

normal phenotypic expression is present when a minimal level of wild type gene product is attained

threshold effect

the heterozygous offspring have a trait that is not exactly like the trait of either purebred parent.

intermediate inheritance

heterozygous offspring show a phenotype that is in between the phenotypes of the two homozygous parents (eg red+white = white)

incomplete (partial) dominance

both alleles in a heterozygous express themselves fully (both traits have a capital letter, but they are different letters)

codominance

a trait controlled by more than one gene

eg - h substance the carbohydrate group present on the surface of red blood cells to which the A and/or B antigen may be added. When unmodified, it results in blood type O

polygenic traits

a rare recessive mutation which prevents someone from synthesizing the complete H substance

FUT1

in humans italicized capital letters are used to name _____ (eg BRCA1)

________ are not italicized (eg BRCA1)

genes, proteins

uppercase letters and superscripts to denote alternative alleles -Example: R¹ and R², L^M and L^N, I^A and I^B

no dominance exists between alleles

one wild type allele is sufficient to produce enough of the essential product to allow survival, but 2 mutant copies is lethal

recessive lethal alleles

cystic fibrosis, sickle-cell anemia, and achondroplasia, are _______ allele disorder

recessive

an autosomal dominant bone disorder that causes dwarfism, the inheritance of two mutant FGFR3 alleles is fatal

achondroplasia

receptor that plays a role in cell differentiation and development

fibroblast growth factor receptor 3 (FGFR3)

mutation in the the β-globin subunit of hemoglobin causes it to form long chains that end up “sickling” the blood cell’s shape making it a poor transporter of oxygen. (homozygous for lethality at a younger age)

• heterozygosity protects against malaria

• parasites cannot grow as well in sickled cells or in the lower oxygen environment

sickle cell anemia

when a single gene affects more than one trait (eg sickle cell anemia)

pleiotropy

autosomal dominant mutation in the gene encoding the connective tissue protein fibrillin

• fibrillin is part of the ECM and is important in most body tissues

• phenotypes: lens dislocation, aortic aneurysm and long limb bones

marfan syndrome

an autosomal dominant disorder, deficient function of the enzyme protoporphyrinogen oxidase.

• cannot metabolize poryphyrin component of hemoglobin

• buildup of porphyrins = red urine, abdominal pain, muscular weakness, fever, a racing pulse, insomnia, headaches, vision problems, blindness, delirium, and convulsions

porphyria variegate

tendency of DNA sequences that are close together on a chromosome to be inherited together

• usually not affect by crossing over

genetic linkage

the production of novel phenotypes by the interaction of alleles of different genes

gene interaction

the phenotype resulting from gene interaction - often a mutation in any one of many developmental genes required for the trait

heterogenous traits

traits are usually influenced by many gene products (eg _________: mutations inthe LRRK2, PARK7, PINK1, PRKN, or SNCA genes)

parkinson

in the substantia nigra die. They normally send signals to the striatum which relays them to cortical neurons that control motor functions

dopaminergic neurons

_________: if the leucine rich repeat kinase 2 (LRRK2) of synuclein alpha (SNCA) gene is involved, this is inherited in an ______________ _________ pattern - _________ activity is disrupted

parkinsons, autosomal dominant, lysosome

__________: if the PARK7, PINK1 (kinase), or PRKN (E3 liagase) gene is involved, this is inherited in an _______ ___________ pattern - one good gene is enough to promote mitochondiral recycling, but it is disrupted if both copies are non-functional

parkinsons, autosomal recessive,

in this condition, mitochondrial function is disrupted in neuron, leading to neuron death

parkinsons

the nonreciprocal interaction between nonallelic genes such that one gene influences the expression of another gene, leading to a specific phenotype. (i.e. the expression of the gene masks or modifies the effect of a second gene)

epistasis

the following is an example of ________: FUT1 gene (H substance production) masks the expression of the A and B blood type alleles

epistasis

a ratio tat is expressed in 16 parts (eg 3:6:3:4) suggests that _ ____ _____ are interacting in the expression of the phenotype

2 gene pairs

genes whose expression is blocked or masked

hypostatic

distinct phenotypes are produced (eg blood types can be A, B, AB, or O, but can’t be anything in between

discontinuous variation

recessive gene masks or suppresses the phenotype of a different gene

recessive epistasis

when a dominant allele at one genetic locus masks the expression of the alleles of a second locus

dominant epistasis

test for determining whether two mutations for a phenotype represent 2 alleles or are variations of 2 different genes

complementation analysis

cross of 2 mutants restores the wild-type phenotype revealing control by 2 different genes

complement

mutations in a single gene - that do not complement each other in a cross

complementation group

________________ groups crossed with any other complementation group will complement each other (think group is same gene)

complementation

the pattern of inheritance resulting from genes located on the X chromosome

x-linkage

having a gene present in a single dose in an otherwise diploid cell (usually applies to genes on the X or Y chromosome in males

hemizygous

these are all examples of _ ______ traits: color blindness, hemophilia, lesch-nyhan syndrome

x linkage

a trait that is expressed in only one sex even though the trait may be X-linked or Y-linked

• the trait appears in only one sex, but it may not occur in all members of that sex

• eg lactation

sex-limited inheritance

____ ________ disease examples: males can have prostate cancer and only females can have ovarian cancer, although both males and females can carry the genes for these conditions

sex limited

a phenotypic expression modulated by the sex of the individual

• a heterozygote may express one phenotype in one sex and an alternate phenotype in the other sex (eg pattern baldness)

sex-influenced inheritance

the percentage of individuals that manifest some degree of a mutant phenotype for a given genotype (eg only 80% of people with mutant allele have disease)

penetrance

the range of phenotypes for a given response (eg allele phenotype is stronger in some individuals and weaker in others)

expressivity

the impact of the collective genome of an organism on the expression of a gene

genetic background

a change in expression of a gene associated with a change in the gene’s location within the genome (eg: a translation or inversion event)

position effect

DNA and protein that is highly condensed, gene-poor, and transcriptionally silent - RNA polymerase cannot access the DNA in this

heterochromatin

DNA & protein that is less condensed, gene-rich, and more accessible to transcription

Euchromatin

a conditional mutation that produces a mutant phenotype at one temperature and a wild-type phenotype at another (eg the enzyme for pigment production is functional only at the lower temperatures present in the extremities, but it loses its catalytic function at the slightly higher temperature found throughout the rest of the body

temperature-sensitive mutation

a mutation expressed only under a certain condition; a wild type phenotype is expressed under certain (________) conditions and a mutant phenotype under other (_______) conditions

conditional mutations, permissive, restrictive

a mutation that alters the metabolic ability of an organism

nutritionally mutations

a mutant microorganism or cell line that through mutation has lost the ability to synthesize one or more substances required for growth

auxotroph

an organism of cell capable of synthesizing all its metabolites from inorganic material, requiring no organic nutrients

prototroph

cannot metabolize galactose

galactosemia

cannot metabolize lactose

• lactose is broken down into galactose and glucose

• if the dietary intake is reduced or eliminated, the detrimental effects may be ameliorated

lactose intolerance

an x-linked recessive disease, due to a mutation in the gene encoding hypoxanthine-guanine phosphoribosyl transferase (HPRT)

• newborns are normal for six to eight months prior to the onset of the first symptoms. few patients live beyond 40 years

• inability to salvage nitrogenous purine bases

• accumulation of uric acid in blood and tissues, mental disabilities, palsy, and self mutilation of the lips and fingers

Lesch-Nyhan syndrome

the severity of symptoms in a genetic-disorder increases from generation to generation and the age of onset decreases from generation to generation

genetic anticipation

a three nucleotide sequence of DNA within the Dystrophia Myotonica Protein Kinase (DMPK) gene is repeated a variable number of times

• DMPK phosphorylates muscle-specific, voltage gated sodium channels

• patients have 50 to 1,000 CTG repeats in most cells that increases repeat number with each generation

Myotonic dystrophy (DM1)

genes present on the same chromosome, causing them to be inherited as a unit

• if they are not separated by crossing over during meiosis

linkage

the exchange of chromosomal sections between homologous chromosomes by breakage and reunion

crossing over

crossing over results in this, which the the process that leads to the formation of new allele combinations on chromosomes

recombination

a gamete containing a new combination of alleles produced by crossing over

recombinant (crossover gametes)

one percent of the expected recombination between 2 genes (on recombination event per 100 crosses - also called centi-Morgans (cM)

one map unit (mu)

Conservation of blocks of sequence within 2 sets of chromosomes that are being compared with each other

synteny

condition in which the body responds improperly to an infection

• immune mediators released into the blood

• causes uncontrolled inflammation, blood clots, and leaky blood vessels

• blood flow is impaired, depriving organs of nutrients and oxygen and leading to organ damage, and death

• bacterial infections cause most cases of this

sepsis

a growth medium containing only the essential nutrients needed to support the growth and reproduction of wild-type strains of an organism

• a C source (sugars), N source, and salts

minimal medium

a cell line that is capable of growth on a minimal medium - wild type strains are usually regarded as prototrophs

prototroph

a mutant cell line that has lost the ability to synthesize substances required for growth

auxotroph

media supplemented with needed nutrients

complete medium

the time period where bacteria are adapting to new conditions (media) and growth is slow

lag phase

bacterial population grows logarithmically

log phase

bacterial population stabilizes as the nutrient supply is depleted - fresh media is needed

stationary phase

the transfer of genetic information between members of the same bacterial species

vertical gene transfer

the transfer of genetic information between members of the different bacterial species

• most bacteria have genes from other species

• drives evolution of bacteria & promotes speciation

horizontal gene transfer