Bio 226 - Final Flashcards

Why did Mendel choose the garden pea for his test crosses?

• Easy to grow

• Short life cycle

• Pollination could be controlled

• Different varieties available

• Types were easily distinguishable

What is a test cross?

Cross between a homozygous recessive and an unknown to determine its genotype

What is the Law of Segregation (first Mendelian law)?

• Alleles of a gene separate independently from each other during transmission from parent to offspring

• The dominant phenotype appears at 100% in the F1 (hybrid genotype)

• The phenotypic frequencies in F2 conforms to 3 dominant: 1 recessive

What are the two principles of Mendel’s first law?

• Principle of Dominance:

  • In a heterozygote, one allele may conceal the presence of another

• Principle of Segregation:

  • In a heterozygote, two different alleles segregate from each other during the formation of gametes

What are the predictions of Mendel’s 1st Law?

1. Reciprocal crosses should yield identical results

• Randomness in allele segregation is independent on the source of the allele

2. Of the plants with yellow seeds in the F2, 2/3 should be Yy and 1/3 should be YY

3. Gametes produced by heterozygote should come at a ratio of 1:1

Which generation directly shows evidence for dominance?

The f1 (hybrid) generation directly suggests dominance

• Cross will consist exclusively of heterozygotes displaying the dominant phenotype for the allele combination in the locus

Which generation directly provides evidence for the independent segregation of alleles?

The F2 generation directly suggests free segregation of alleles

• Cross shows the outcome of segregation of alleles in the F1 gametes

What are the two basic probability rules?

1. Probability of two independent events occurring together

2. Probability that at least one of the two events will occur at all

If two events are independent, how is the probability of them occurring together determined?

Multiplicative Rule

• Probability of two independent events occurring together is the product of the separate two probabilities

If two events are independent, how is the probability of only one of them occurring determined?

Additive Rule

• Probability of one or another event occurring is the sum of the separate probabilities

What are the F1 results of a dihybrid cross?

100% dominant trait phenotype and heterozygote genotype

What are the results of the F2 results of a dihybrid corss?

• 9:3:3:1

  • 9 dominant parental phenotype

  • 3 and 3 recombinant phenotypes

  • 1 recessive parental phenotype

What is the Law of Independent Assortment (second Mendelian law)?

• Alleles of two or more genes segregate independently during transmission from parent to offspring

• The two dominant phenotypes appear at 100% in the F1

• In the F2, 4 phenotypic classes are present (2 parental, 2 recombinant - 9:3:3:1)

What is a Chi-Square Test?

• Tests whether a sample collected (observed) can be used to support a hypothesis for a prediction (expected)

• Tests against the null hypothesis

  • Reject when over critical value

How many chromosomes in human genome?

23 pairs of chromosomes

• 22 pairs of autosomes

• 1 pair of sex chromosomes

What are pedigrees?

• Diagrams that show the relationship among members of a family

• Represent the inheritance pattern of a specific condition

What is haplosufficieny?

When a heterozygote makes enough normal product encoded by the wild type allele and has the normal phenotype

What is the inheritance patterns of an autosomal recessive trait?

• Parents do not need to be affected (carriers)

• Unless intermarriage occurs, the disease allele will likely be hidden

• All children of an effected parent (homozygous) and a homozygous normal parent will be unaffected carriers

• Can appear to be ‘skipping’ populations

What is the inheritance pattern on autosomal dominant traits?

• When one parent is affected (heterozygote) and the other is not, half the children will be affected

• Unaffected people cannot be carriers

• Children of two unaffected parents will also be unaffected

• Two heterozygote affected parents can potentially have normal children

• Typically does not ‘skip’ generations

What is meiosis’ role in random segregation?

Provides the randomness expressed in Mendelian ratios

What is meiotic shuffling?

Cellular mechanisms that dictates inheritance patterns

What is the chromosomal theory of inheritance?

• Genes are not inherited in isolation but as part of a larger structural units (chromosomes) shared with other genes with which they segregate

How does the SRY gene impact sex?

• Determines male reproductive development

• Without it, the female reproductive pathway occurs as the default pathway

What is a non-disjunction event?

• Failure to correctly separate during anaphase causing defects in the number of chromosomes inherited

  • Generates gametes that carry two homologs or none

What are the characterisitcs of x-linked recessive traits?

• Nearly all affected will be male

• Carrier females are usually phenotypically normal but transmit the recessive allele to half of their children

• Half the sons of a carrier are affected and half the daughters are carriers

• All sons of an affected female will be affected, all daughters will be carriers

• An affected male cannot transmit to the sons, all daughters will be carriers

What are the characteristics of X-linked dominant traits?

• No carriers

• Affected males transmit to all daughters but no sons

• Affected heterozygote females transmit to half the children regardless of sex

• Affected homozygous females transmit to all children

• More common in females

What is monoploidy?

The haploid set of chromosomes of a species (n)

What is euploidy?

A chromosome number that is exactly the multiple of the monoploid number of chromosomes

What is polyploidy?

A change in the number of copies of an entire set of chromosomes

What is aneuploidy?

When one or more chromosomes are missing or in excess

What is an autopolyploid?

All the chromosomes originated from the same organism

What is an allopolyploid?

One set of chromosomes originated from one organism and the other from another

What are monosomies?

One missing chromosome

• Most die in utero

• Viable on X chromosomes - causes Turner Syndrome

What are trisomies

One extra chromosome

• Embryonic lethal

• Viable causes Klinefelter syndromes (XXY) or Down Syndrome (chromosome 21)

What is gene imbalance?

• Unbalanced amounts of genes disrupts metabolic activity

  • Ex: Generates too much inhibitor

• Disrupts the relative amounts of proteins needed to correctly perform a given function

When is gene imbalance less detrimental?

In smaller chromosomes (less genes, less pathways)

• I.e chromosome 21

Also on sex chromosomes

How does the imbalance of Y chromosomes differ from X chromosomes?

• Imbalance of Y effects fertility

• Imbalance of X has minor effects

  • X chromosome has naturally evolved to be dosage compensated between the two sexes

  • Female embryos can silence an X chromosome

What are some causes of non-disjunction?

• No crossing over occurring during meiosis 1

• Sister chromatids do not separate during meiosis 2

Where does most non disjunction occur?

Maternally during meiosis 1

• Women’s eggs exists dormant for many years - can deteriate

  • Older mothers have increased odds of trisomy

What are the types of chromosomal reaarragements?

• Translocation

  • Change in location

• Deletion

  • Loss of genetic material

• Inversion

  • Movement of genetic material

• Duplication

  • Double genetic material

How do chromosomal rearrangements occur?

• DNA damage

  • DNA double strand breaks

• Recombination mistakes

  • Crossover between repeated sequences

What is the difference between balanced and unbalanced chromosomal rearrangements?

• Balanced:

  • Changes do not result in gain or loss of genetic material

  • Gene dosage is not effected

  • Bipolar gene attachment

  • Viable

• Unbalanced:

  • Changes result in loss or gain of genetic material

  • Results in gene dosage problems

  • Multipolar gene attachment (chromosome breaks b/c multiple centromere) or no attachment (spindles fail to capture b/c no centromere)

  • Unviable

What are the effects of deletion on a phenotype?

• Exposes haploinsufficiency

• Unmasks recessive mutation

  • Causes pseudo dominance

What are the ffects of duplication?

• Can cause genetic disorders

• Are a normal evolutionary force for genome building

What are the effects of inversion?

• Disrupts mechanics of chromosome pairing in meiosis

  • Causes chromosomal loops that disrupts segregation

• Can change gene function or make hybrid genes

What are the effects of translocations?

• Can be viable if no gene is effected by the breakpoint and the centromere is not effected (reciprocal)

• If break point move centromere, will not be viable

What are the types of genetic interactions?

• Intra (allelic):

  • Dominance/ recessivness, co dominance, incomplete dominance

• Environment interaction:

  • Penetrance, expressivity

• Extra:

  • Supression, enhancement, pathways

What is a dominance hierarchy?

• Progressive loss of function in dominance relationship

• Wildtype —> Hypomorphs —> null mutant

What is incomplete dominance?

• Appearance of a third phenotype that blends tow parental ones

What is co dominance?

• More than one allele is dominant

• Heterozygote displays both parental phenotypes

  • Ex: Blood type AB

What is variable penetrance?

• Presence of the same genotype with different phenotypes

• Will either express the determined phenotype or not express it at all

• No longer 100% expression

What determines penetrance?

• Modifier genes

• Environmental factors

• Allelic variation

• Complex genetic and environmental interactions

What is variable expressivity?

• The degree or intensity that a gene is expressed

• Same genotype, variable mutant phenotypes

What is pleiotropy?

• One gene controlling two or more unconnected phenotypes

What ratio indicates dominant lethal alleles?

2 dominant: 1 recessive

What is polygenic inheritence?

• Many genes affecting the same phenotype

How can you test whether a phenotype is monogenic or polygenic?

• Complementation test

  • Failure to complement indicates allelism (one locus involved)

  • Complementation indicates non-allelic mutants - more than one gene is responsible to the same phenotype

How can alleles of a gene supress or enhance the effect of alleles of another gene?

• Supressor mutations

  • The presence of a second mutation reverses the effects of the first

• Enhancer mutations

  • The presence of a second mutation increases the effect of the first mutation

What is the one gene - one enzyme theory?

Every enzymatic step involves one enzyme, therefore one gene

How are the number of steps (genes) in the pathway determined?

Complementation test

• Reveals groups of allelic mutations

• Number of complementation groups = number of steps in the pathway

  • Fusion of two different mutant strains creates a diploid

  • Tests if the diploid survives without supplementation

• + complementation = complementing alleles (non allelic mutants)

• - complementation = failure to complement (allelic mutants)

How can you determine which step is the pathway blocked in a mutant?

Supplementation Tests

• Supplementation with substrates downstream from the block will rescue the defect

What are the ratios of the gene interactions?

• Additive gene action: 9:3:3:1

• Complementary gene action: 9:0:0:7

• Duplicate gene action: 15:0:0:1

• Dominant epistasis: 12:0:3:1

• Recessive epistasis: 9:3:0:4

What is additive gene action?

• 2 genes influencing the same phenotype

  • F1 will have different phenotype than parents

  • Does not follow mendelian rules because genes are not independent

  • Mendelian like distribution (9:3:3:1), each phenotype is distinct for the same trait

• I.e: Genes A and B are needed in different pathways to produce different end products

What is complementary gene action?

• Genes acting in the same pathway, 2 genes 2 phenotypes

  • No recombinant offspring occurs (9:7 ratio)

  • Dominance of both traits = 1 phenotype, recessiveness of at least one trait = other phenotype

  • Homozygous recessive acts as a block, preventing expression of other phenotype by blocking the development of one or both enzymes

• 2 enzymes act in different steps of the same pathway to promote protein synthesis

What is duplicate gene action (redundancy)?

• Dominant alleles of both genes overpower each others recessive alleles

• Domiant alleles of both genes alone produce the same phenotype

  • Presence of at least one dominant allele guarentees wild type expression - need fully homozygous to be mutant

  • Act as pseudoalleles

  • 15:1 ratio

  • Both pathways, regardless of which enzyme is used, produces the same product

What is epistasis?

• Alleles of one locus are supressed by alleles of a different locus

  • Mutant allele of one gene overrides the phenotypic effect of a mutant allele of another gene when both are present in the same genotype

  • Involves inter-allelic gen interaction

What are the types of epistasis?

• Recessive epistasis:

  • When the recessive allele of one genes masks the effect of the allele of the second gene

  • 2 genes, 3 phenotypes (9:3:4)

• Dominant epistasis:

  • When the dominant allele of one gene masks the effect of the second gene

  • 2 genes, 3 phenotypes (12:3:1)

Which force is better at generating recombination, assortment or C.O?

Assortment because C.O rarely occurs between two chromosomal loci

How does genetic linkage effect Mendelian laws?

• Major exception to the second law

• Accounts for most of the deviation in F2 phenotype proportion

  • Increased proportion of parental phenotypes

What happens when no crossing over occurs?

100% parental gametes - no recombination

What happens if C.O happens before DNA duplication?

100% recombinant gametes

What happens of C.O happens after the completion of meiosis I?

100% parental gametes

What happens if meiosis occurs during meiosis I?

• 50% parental gametes 50% recombinant gametes

• C.O involves 2/4 chromatids

What happens during a double crossing over?

Will have all parental phenotypes as if no C.O happened

• Even number C.Os between 2 loci will regroup the parent information along the chromosome and be undetectable

• Still carries recombinant information, but the information is ‘cancled out’

What is the recombination frequency (RF) in Mendelian cases?

• Genes assort independently by random chance

• RF = 50%

What is the RF in gene linkage cases?

• Genes do not assort independently, through C.O

• RF < 50%

What are the two possible combinations of mutant phenotypes in gene linkage?

• Coupling (cis)

  • Both recessive alleles in f1 come from one parent in P0

  • I.e homozygous parents

• Repulsion

  • One recessive allele in F1 comes from each P0 parent

  • I.e heterozygous parents

What determines the frequency (likelihood) of C.O?

The physical distance between the genes on the same chromosome

• RF increases as distance between genes increases until RF = 50%

When are genes considered to be linked?

When genes have RFs < 0.5

• Must be on the same chromosome - syntenic

  • Physically together and genetically linked

• Recombination between 0 and 50%

When are genes considered unlinked?

When genes have RFs = 0.5

• Likely to be on different chromosomes - non-syntenic

When can genes be syntenic but unlinked?

When genes have RFs > 50

How is gene distance related to C.O events?

Distance between two points of a chromosome is equal to the average number of crossing over between them

• Mapping unit = % recombination

Why is recombination events underestimated when calculating RF?

• Recessive information will be hidden in dominant parental genotypes

  • Recombinant gametes can produce parental phenotypes because of dominance

Why is the DR class important when finding RF?

• Because the double recessive class cannot hide

• Can be used to derive the other gametic and phenotypic frequencies

What is crossover interference?

A process that prevents multiple C.Os occurring close together

• The occurence of one recombination event inhibits subsequent ones in the same region

What can be assumed if the Chi Square value is greater than the critical value?

Gene linkage is likely behind the interaction - proportions are not following mendelian ratios

What are the limitations of genetic mapping?

• RF becomes less reliable to predict genetic distances the farther the genes are because of multiple crossing over

  • Corrections need to be made when determining the distance of genes far apart

• Over 50 cM (syntenic, unlinked), distances cannot directly be calculated, they need to be inferred based on shorter distances using linked markers

What are the 3 mechanisms of gene action and transmission?

• Replication

• Transcription

• Translation

What is the process of the Central Dogma?

• DNA gets transcribed into RNA

• RNA gets translated into amino acid chain

• Amino chain folds into protein

The original Francis Crick theory of central dogma stated…

• DNA is unidirectionally transferred to RNA during transcription and to proteins during translation

• DNA and RNA could be self regulating but not proteins

How were new ways to transduce genetic information discovered?

RNA viruses

What did the RNA viruses prove?

1. RNA can replicate itself

2. RNA can be retrotranscribed to DNA

How were RNA viruses used to prove that RNA is self replicating?

• Used RNA viruses that use antisense RNA - no DNA

  • Used their RNA as a template to generate sense mRNA for protein synthesis

  • Used RNA as a template to replicate its own genome material

• Process of RNA-dependent RNA polymerase enzymes to turn antisense into sense, then back into antisense

How were RNA viruses used to prove that RNA can be retrotransribed into DNA?

• Used RNA viruses that use sense RNA that produce a DNA copy of their genome

  • Accomplished using retro (reverse) transcriptase enzyme to polymerize DNA from RNA

  • DNA then integrates host’s genome

What are prions?

• A protein that, when folded incorrectly, triggers prion diseases that are self-reproducing

• The misfolded prion becomes insoluble and causes neural death

What is the modern understanding of the central dogma?

• DNA

  • Self polymerizing

  • Becomes RNA through RNA polymerase

• RNA

  • Self replicating through RNA-dependent RNA polymerase

  • Can turn into DNA by retrotranscriptase

  • Can turn into proteins by aminoacyltransferase

• Protein

  • Self replicating through prions

What is the original self replicator molecule?

RNA

How does the transfer of genetic information differ in prokaryotes and eukaryotes?

• Prokaryote

  • Anuclear

  • Transcription and translation occur in cytoplasm

  • Not timely separate

• Eukaryote

  • Transcription and translation occur in different cell compartments

  • Can be timely separate

Where is mRNA made?

• Synthesized in nucleus, transported to cytoplasm

What is the lifecycle of mRNA

• mRNA synthesis is rapidly induced and rapidly used up before its degradation

• mRNA has a very short life cycle