Mutation II Flashcards by Anna Stone

describe chromosomal mutations

insertions and deletions on a massive scale, often affecting dozens of genes

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4 types of chromosomal mutations

deletions, duplications, inversions, translocations

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what do chromosome structure mutations require

require breaking and rejoining of chromosomal DNA (deletions)

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describe intrachromosomal mutations

occurs between parts of the same chromosome (deletions and duplications)

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describe inversion. where does it occur?

changing the order of genes (can occur between maternal and paternal homologous chromosomes)

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describe translocations. where does it occur?

a chunk of one chromosome gets exchanged for a chunk of another chromosome making hybrid chromosomes (can occur between non-homologous chromosomes)

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how does unequal crossing over lead to chromosome structure mutations?

unequal crossing over between homologous chromosomes during meiosis can lead to duplications and deletions (often occurs at repetitive sequences the cell thinks are homologous)

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what is recombination? how might it lead to chromosome structure mutations?

recombination is intrachromosomal crossing over (rare, happens during meiosis) & it occurs at repetitive sequences the cell thinks are homologous which leads to deletions or inversions

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what may cause double stranded DNA breaks? how does this result in chromosome structure mutations?

ionizing radiation causes double stranded DNA breaks, repair of these breaks can lead to translocations

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4 potential consequences of chromosome structure mutations

1) can possibly do nothing (exchanging of entire genes)
2) variety of changes in gene expressions (genes placed next to new CREs, CREs lost or duplicated)
3) created truncated proteins by causing frameshifts or deleting exons
4) create new proteins with new functions by duplicating exons or combining exons from different genes

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describe chromosome number mutations

changes in the number of chromosomes in the genome

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what is n? n for humans? what is 2n?

n is the number of chromosomes in a gamete (humans are n = 23), 2n is diploid

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describe aneuploidy

number of chromosomes is not an exact multiple of n

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describe aberrant euploidy

number of chromosomes IS an exact multiple of n that is NOT TYPICAL for the organism

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describe monosomic aneuploid

(2n-1) mammalian embryos typically die

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describe trisonomic aneuploidy

(2n+1) most common in mammals

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why can trisomies have worse phenotypic effects than aberrant euploidies?

because trisonomies often create imbalances in the ratios of interacting proteins (many proteins have to bind to other proteins to stay in solution, without binding partners, these proteins form toxic protein aggregates)

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what type of chromosome structure mutation could produce a phenotype that mimics a trisomy?
a) translocation
b) inversion
c) duplication
d) deletion
e) more than one answer correct

e: c & d are correct

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in humans, most aneuploidies are embryonic ____

lethal

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the only viable human monosomy

affects the X chromosome

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only viable human trisomies

chromosomes 13, 18, 21, X and Y

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most eukaryotes are ___, except for _____

diploid; sex cells (eggs and sperm)

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describe monoploid

whole organism is haploid

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describe polyploid

there are more than two copies of each chromosome; triploid (3N), tetraploid (4N)

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why is monoploidy rare? where is it seen?

rare because it reveals many recessive lethal mutations (no backup copy of the gene); it is seen in some social insects

where is polyploidy seen?

1/3 known plant species (alfalfa, coffee, peanuts, apples, pears, strawberries), some fish, frogs, lizards, one rat

is polyploidy possible in humans?

no, always lethal

main cause of aneuploidy

chromosomal nondisjunction during mitosis or meiosis (when homologous chromosomes or sister chromatids don’t separate)

what happens when chromosomal nondisjunction occurs during meiosis and the resulting gamete is fertilized?

the zygote will have aneuploidy

cause of polyploidy

complete nondisjunction (if during meiosis and the resulting gamete is fertilized, the zygote is polyploid)

what percent of human zygotes have the wrong number of chromosomes?

describe functional mutations

mutations that alter the phenotype (form and function) of an organism

what types of DNA mutations can be functional mutations?

all types of DNA sequence mutations in any part of the genome

describe a gain-of-function mutation in protein-coding exons

causes the gene product (protein) to do something new

example of a gain-of-function mutation in a protein-coding exon

a mutation in a transcription factor gene that allows the T.F. to bind to a new TBS

describe a gain-of-function mutation in a CRE

causes the gene product to be expressed at a higher level of in a new place

example of a gain-of-function mutation in a CRE

a mutation in an enhancer causes more keratin to be expressed in hair follicle cells

how common are gain-of-function mutations?

rare - very hard to make something work better

how common is a loss-of-function mutation?

most common type of functional mutation - many more ways to break a system

a complete loss-of-function mutation is called:

null mutation

describe a loss-of-function mutation in protein-coding exons

causes the gene product to not work properly, if at all

example of a loss-of-function mutation in protein-coding exons

a mutation causes the enzyme that makes melanin to no longer function, resulting in albinism

describe a loss-of-function mutation in a CRE

causes the gene product to be expressed at lower levels, or not at all

example of loss-of-function mutations in a CRE

a mutation in a CRE of the gene the encodes the melanin synthesis enzyme results in different coat shades

describe housekeeping genes

genes used by all cells to perform basic functions

examples of housekeeping genes

aminoacyl tRNA synthase (ARS), DNA polymerase, rRNA, histones, various enzymes

what does a complete loss of function in housekeeping genes lead to?

death of embryo or cells

what does a partial L.O.F. or G.O.F. in housekeeping genes lead to? why?

severe genetic diseases affecting many organ systems, because these genes are highly pleiotropic

describe cell cycle checkpoint genes. what sort of things do they sense?

encode a variety of proteins that monitor cell health and regulate cell division (sense things like DNA integrity, viral infection, cell cycle progression, cell density, cell anchorage)

examples of cell cycle check point genes

cyclins monitor cell cycle progression, BRCA monitors DNA

what happens when there is a complete loss of function in cell cycle checkpoint genes?

death of embryo, higher risk of cancer

what happens when there is a partial loss of function in cell cycle checkpoint genes?

higher risk of cancers

what kind of mutations does cancer usually require?

simultaneous L.O.F. mutations in several (4-6) check point genes, reflects the redundancy of the check point system

people who inherit 1 or 2 L.O.F. mutations in check point genes have a higher chance of what?

getting a certain cancer

purpose of BRCA genes

encode multifunctional check point genes that pause cell division, induce apoptosis when DNA is damaged, and are essential for repairing damaged DNA

where are BRCA1 and BRCA2 expressed in high levels?

breast and ovaries

women with BRCA1 or BRCA2 loss-of-function mutations have up to a ___ risk of developing breast cancer by age 9

90%

BRCA1 and BRCA2 mutations are so predictive that women often opt for:

preventative breast removal (mastectomy)

what happens when there is a gain of function mutation in cell cycle check point genes?

no cancer in big mammals and armadillos because of duplications of check point genes

what happens when there is a L.O.F. mutation in transcription factor genes and/or intercellular signaling receptor and ligand genes?

non-viable developmental defects including loss (or duplication) of whole body regions, tissues, or cell types

consequence of mutations of transcription factor genes (Hox genes)

can cause body regions to take on the wrong identity during development, called homeotic transformations

consequence of mutations in intercellular signaling ligand and receptor genes

disrupts morphogen gradients and causes patterning defects

describe patterning defects

losses or expansions of whole regions or parts of the body

consequence of mutations in intercellular signaling ligand genes (such as Sonic Hedgehog Hog SHH)

loss of SHH causes loss of midline structures and cyclopia (cyclops) & can also cause homeotic transformations

Sonic Hedge Hog gene function

creates a morphogen gradient that patterns the embryo from medial to lateral & creates a morphogen gradient the patterns the forming of hands and feet

describe when developmental regulators (intercellular signaling receptors/ ligands and transcription factors) are used during development

re used many times during development and are thus highly pleiotropic

is SHH pleiotropic? consequence?

yes, SHH is used to pattern limbs, gut, and brain as well; mutations in SHH can cause a range of phenotypes including cyclopia, polydactyly, brain defects, and gut defects

describe CREs for developmental regulators. why is this important for mutations in CREs for developmental regulators?

developmental regulators have separate CREs controlling their expression in different tissues; mutations in tissue-specific CREs can cause small changes in expression limited to that tissue

major source of morphological variation between and within species

mutations in the CREs of developmental regulators

consequence of partial L.O.F. or G.O.F. mutation in tissue specific effector genes

tissue-specific genetic diseases, and other tissue-specific traits that follow simple mendelian inheritance patterns

examples of tissue specific effector genes

hemoglobin, heart muscle actin, pigment synthesis enzymes

examples of genetic diseases caused by L.O.F. mutations in tissue specific effector genes

sickle cell anemia (hemoglobin) Duchenne muscular dystrophy (dystrophin protein in muscle cell membrane) Cystic fibrosis (calcium ion channel in lung epithelium)

examples of “non-disease” like traits that are a consequence of L.O.F. mutations in tissue specific effector genes

coat/eye color (mutations in tyrosinase melanin production enzyme) flower color (mutations in “Dfr” red pigment synthesis enzyme