Lecture 1.2: mutation + single gene Flashcards
1
Q
1) Define polymorphism
2) Is this its only defining characteristic?
A
1) Two or more versions of an allele, with each comprising at least 1% of the population
2) Yes
2
Q
Define locus and what it looks like when it’s large or small
A
1) “Locus” (Latin for location) is a segment of DNA occupying a particular position or location on a chromosome (plural “loci”)
-May be large: a segment with many genes
-May be tiny: one base in the DNA code
3
Q
1) Alternative versions of a locus on the DNA code are called what?
2) What do changes between these result from?
A
1) “Alleles”
2) Mutation
4
Q
1) The most common version (accounting for more than 50%) is called the _________________ or _____________ allele”
2) Alternative to this are the ___________ or ___________ alleles
A
1) “wild type” or “common allele”
2) “mutant” or “variant”
5
Q
1) Define genotype
2) Define phenotype
A
1) The genetic material in a person – in a specific locus the two alleles occupying that locus on two homologues
2) The expressed physical traits of the genotype
6
Q
1) Define mutation
2) Will it always effect fitness to the envt?
3) What mediates it?
A
1) Random change to the DNA structure
2) May or not effect fitness to the environment
3) Selection
7
Q
List the 3 categories of mutation (largest to smallest by size)
A
1) Chromosomal mutation
2) Regional or subchromosomal mutations
3) Gene mutation
8
Q
Define chromosomal mutation and its outcome
A
Mutation accounting for all or most of a chromosome
-Most always leads to disease or death
9
Q
1) Define Regional or subchromosomal mutations
2) Define gene mutation. Is it always a big deal?
A
1) The middle ground between gene mutation and chromosomal
2) Alteration of involving substitution, deletion, or insertion of DNA – from single nucleotide to arbitrary limit of 100kb
-Can be benign or a “big deal”
10
Q
1) Our cells make what from DNA?
2) The alterations that wind up on the _________ strand are the mutations we are talking about
3) In order to create a phenotypic difference, where does the DNA mutation have to be carried over to?
A
1) RNA
2) protein
3) To RNA and translated into the protein
11
Q
True or false: Some mutations occur in DNA or RNA only – and sometimes there’s no change in the protein!
A
True
12
Q
What 3 questions should you ask to figure out if a change in DNA structure will correspond w a change in protein?
A
1) Does the mutation occur in a coding segment?
2) Does it substantively change the codon?
3) Does the change in polypeptide composition change the function of the protein?
13
Q
1) Define Single Nucleotide Polymorphisms (SNPs)
2) What does it usually have?
3) Where do most occur?
A
1) Multiple versions of nucleotide base at single location “substitution
2) Usually has but two alleles
3) Non-coding portions of DNA
14
Q
1) More than 100K ________ SNP’s have been discovered
2) Half of these do not alter the amino acid sequence (called “________________”)
3) Those that alter amino acid sequence are “________________”
A
1) exonic
2) synonymous
3) nonsynonymous
15
Q
List 2 significant changes caused by Single Nucleotide Polymorphisms (SNPs)
A
1) Altering or introducing a stop codon
2) Altering a splice site where introns/exons are altered
16
Q
1) How many base pairs can Indels (Insertion / deletion polymorphisms) occur in?
2) How many alleles do most “simple” indels have? What does this mean?
3) What is another type of indel besides “simple”? What are these?
A
1) As few as one base pair, and as many as ~1000
2) Two; basically, the presence or absence of the inserted/deleted segment
3) “Microsatellite”; have multiple short repeats of the inserted segment
17
Q
1) Give an example of a microsatellite indel
2) What does this make? What are these called?
A
1) Instead of a single instance of TGT, you see TGTTGTTGTTGTTGT
2) Many different alleles, depending upon how many repeats there are. Called STR polymorphisms
(“short tandem repeat”; tandem means “length”)
18
Q
1) What can be unique and used to identify individuals and families
2) Microsatellite loci are known to researchers and number in the _____________
A
1) Microsatellite indels
2) thousands
19
Q
What is involved in DNA fingerprinting?
A
Microsatellite indels
20
Q
1) Mobile Element Insertion Polymorphisms consist of what? Give examples
2) What happens to these? What is this called?
3) What is this process called? What is it similar to?
A
1) Repetitive elements (think Alu and LINE)
2) Transcribed into RNA, then reverse transcribed back into the DNA code, but at a different locus; retrotranscription
3) Insertion (i.e. transposition); processed pseudogenes
21
Q
1) What are Copy Number Variants?
2) What are the largest of these called?
3) The allelic variation comes from what?
A
1) Up to hundreds of thousands of base pairs long
2) “Segdups” (segmental duplications)
3) The number of copies
22
Q
Regarding copy number variants:
1) True or false: The larger the number of copies inserted, the more variation
2) If these do include genetic material, what can they do? Why is this a big deal?
A
1) True
2) Alter gene dosage; it’s like giving yourself multiple copies of a given gene
23
Q
Give an example of a copy number variant
A
Down syndrome
24
Q
1) Define inversion polymorphism
2) When does it often happen?
A
1) A portion of the sequence is “flipped around”
2) During recombination
(recombination is the same thing as “crossing over”)
25
1) What are the two general types of inversion polymorphisms?
2) What can inversion polymorphisms result in?
1) Pericentric (includes centromere) vs paracentric (doesn't)
2) Duplication or deletion of DNA located between regions of homology, causing genetic disease
26
List 4 origins of mutations
1) DNA replication
2) DNA repair
3) DNA recombination
4) Chromosome segregation
27
What are mutations called when they happen in the gametes? What about in the body?
Germline; somatic
28
1) Many chromosome mutations are produce a change in the number of what?
2) What is this caused by?
3) What does this result in? Maternal or paternal?
4) In what chromosomes is this nearly always lethal? Why?
1) Chromosomes
2) Chromosome missegregation during meiosis I or II
3) Aneuploidy; maternal or paternal (often maternal)
4) Autosomal; "gene dosing"
29
1) Give 3 examples of regional mutations. When do all of these predominantly happen?
2) Give an example of where this can happen
1) Large duplications, deletions, or inversions; during recombination
2) At spontaneous breaks in the DNA
30
Single gene mutations:
Include base pair substitution, indels, can occur in what two ways?
1) During DNA replication
2) After failure to repair damaged DNA
31
1) Between 10,000 and 1 million nucleotides are damaged per ___________ per _____________.
2) Give 3 reasons for nucleotide damage
1) per cell per day
2) Spontaneous processes in the cell, reactions with chemical mutagens in the environment, exposure to UV or ionizing radiation
32
1) "Inserting a base other than the correct complementary one" is the definition of what?
2) How often do these errors in base pairs occur?
3) What is DNA proofreading?
1) DNA replication errors
2) 1: 10 million
3) Repair enzymes recognize which strand contains the incorrect base and replaces it with proper one
33
1) 99.9% of DNA replication errors are resolved by what?
2) How many errors are there then?
1) DNA proofreading
2) Less than one error per cell division
34
Single nucleotide substitution or “point mutation” may lead to one of what two mutations?
“Missense mutation” or “nonsense mutation”
35
1) When mutations alter the genetic code in a “minor way”, they're _____________ mutations, though they need NOT always result in change in function of the protein.
2) What may be wrong with the protein?
1) missense
2) May not work properly, may be unstable and rapidly degraded, or may not localize in the right spot in the cell
36
1) What type of nucleotide substitution mutation disrupts the code enough that the protein is unusable?
2) What does this frequently occur due to?
1) Nonsense mutations
2) Premature or otherwise altered “stop” codon
37
1) The change in the amino acid sequence in sickle cell anemia causes what?
2) What is the change in the AA sequence?
1) Hemoglobin molecules to crystallize when O2 levels in the blood are low. RBCs get sickle and stuck in small blood vessels.
2) TA to AT changes glutamic acid to valine
38
Missense Mutations in Beta Globin Gene:
1) What is the order of the normal HBA sequence in DNA, mRNA, and in AAs? (normal function)
2) What abt in HbS (mild to moderate severe hemolytic anemia)?
3) What abt in HbC (mild anemia)?
4) What abt in Hb Makassar?
1) GAG, GAG, Glu
2) GTG, GUG, Val
3) AAG, AAG, Lys
4) GCG, GCG, Ala
39
During what part of RNA transcription do errors happen?
What are the 2 classes of mutation here? Describe each
Splicing:
1) Introns must be excised and exons spliced together
-This requires nucleotide sequences at 5’ donor site and 3’ acceptor site
-Splicing can be disrupted or broken if mutations occur in either one
2) Base substitutions may also create alternative donor-acceptor sites for splicing
40
What can both kinds of mutation during splicing affect?
The functionality of the end-product protein
41
Frameshift mutations: When the insertion / deletion number of nucleotides is not a multiple of three, what happens?
Everything downstream is messed up
42
1) What makes dynamic mutations unique?
2) What may these mutations involve?
1) In most cases, once a mutation occurs it is stable when transmitted from one generation to the next; in dynamic mutations, the mutation **changes** from generation to generation
2) Amplification in a simple nucleotide repeat sequence
43
Dynamic mutation:
Often the wild type allele is polymorphic with varying number of tandem repeats, however, the _____________ expands as it is passed down in some families, causing abnormalities of gene expression
number
44
Where will mutation persist in mosaicism?
In the descendants of that cell
45
1) Define placental mosaicism
2) Define somatic mosaicism
3) Define germline mosaicism
4) When does segmental mosaicism occur? Give an example
1) In the extraembryonic tissue but not in baby
2) In the body and not gametes
3) In the germline only
4) Only part of the body is affected; neurofibromatosis 1
46
True or false: Mosaicism might and will occur due to X-inactivation
True
47
List 4 different types of mosaicism
1) Placental
2) Somatic
3) Germline
4) Segmental
48
1) Define frequency (in the medical sense)
2) ______________ is sometimes used to refer to the frequency of mutations per se
1) Frequency of mutations per disease locus per generation is considered
2) “Genetic load”
49
How do you track the rate of disease-causing gene mutations; i.e. what 3 things make the frequency traceable?
1) You have to look at incidence of new cases not present in mom or dad
2) Disease has to be caused by single mutation
3) Has to be evident in baby
50
1) What kind of mutation is achondroplasia? What does this mean?
2) Is it dominant or recessive? What does this mean?
1) Gain of function mutation; altered gene product has *new* function
2) Autosomal dominant; when you’ve got it, you display it
51
1) Is achondroplasia a missense or nonsense mutation? Describe where it comes from
2) Achondroplasia is a De novo mutation in germ line of one parent. Which parent is it usually? Why?
3) Will people with achondroplasia mutations always display it? Explain
1) Missense mutation; resulting from substitution of G > A or G > C, which results in the substitution of one Glycine for Arginine
2) Happens almost exclusively in the paternal side because DNA in sperm has undergone far more replication cycles than DNA in the ova
-Greater opportunity for de novo errors due to the sheer number of replications
3) Yes, bc it's an autosomal dominant disorder
52
Clinical features of achondroplasia:
1) What's its age of onset?
2) Describe its phenotype
3) What is it the most common form of?
1) Age at onset: prenatal
2) Rizomelic short stature, megalocephaly, & spinal cord compression
3) Human dwarfism
53
1) FGFR3 protein is ____________________________ receptor that binds to ______________ growth factors.
2) Binding of growth factors there in endochondral bone regulates what?
1) transmembrane tyrosine kinase; fibroblast
2) Proliferation of chondrocytes
54
When mutated, constitutive activation of FGFR3 inappropriately inhibits chondrocyte proliferation in the growth plate.
This leads to what in the long bones and what in the other bones?
Shortening of the long bones, abnormal differentiation of other bones
55
1) List some complications of achondroplasia
2) What are some less common complications?
3) What can midface hypoplasia associated w achondroplasia cause?
4) How can achondroplasia lead to hydrocephalus?
1) Delayed motor development secondary to combination of hypotonia, hyperextensible joints (not in elbows), mechanical difficulty balancing large heads
2) Foramen magnum stenosis leading to brainstem compression
3) Dental crowding, OSA, and otitis media
4) Narrowing of jugular foramina
56
1) What are the 2 ways to Dx achondroplasia?
2) How is it managed?
1) Radiograph or clinically
2) Anticipating and treating complications
57
1) True or false: Achondroplasia meets conditions for tracking disease present mutations
2) What type of mutation disease is achondroplasia?
3) What is pretty unique about it?
1) True
2) Single point mutation
3) It always shows up when present; To have such a clear-cut cause is extremely uncommon
58
Achondroplasia:
1) What do is the risk of inheritance in *subsequent* children of unaffected parents?
2) How about offspring of affected individual?
1) Same odds you started with (small) since you're not a carrier
2) 50%
59
1) Define homozygous
2) Define heterozygous
3) Define compound heterozygous
4) Define hemizygous and give an example
1) Having a pair of identical alleles
2) Having two different alleles – one mutant and one wild type
3) Having two mutant alleles
4) Only one allele (MC a male with the mutant allele on single X chromosome)
60
What terms don't apply to mitochondrial DNA?
Homozygous, heterozygous, compound heterozygous, hemizygous
61
1) What type of disorder did Mendel observe? Define this
2) What are the 3 typical patterns this type of disorder usually can have?
3) Serious disorders in this category effect 1 in ________ neonates and cause ____% of pediatric hospitalizations
1) Single-gene disorder: One determined primarily by the alleles at a single locus; follow the typical patterns
2) Autosomal recessive, autosomal dominant, X-linked
3) 1 in 300; 7%
62
1) What does expressivity refer to?
2) When is expressivity variable?
1) Severity of expression
2) When persons with the same genotype have different severity of symptoms
63
When frequency of expression is less than 100% - in other words, when at least someone with the genotype completely fails to demonstrate disease- it is said to show what kind of penetrance?
“reduced” or “incomplete”
64
Pedigrees:
1) What do empty squares and circles mean?
2) What do fully filled in squares and circles mean?
3) What do squares and circles with dots in the middle mean?
1) Unaffected male (square) and female (circle)
2) Affected male and female
3) They carry the disease but don't show it ("obligate carrier")
65
1) True or false: Single-gene disorders have classic inheritance patterns
2) How should you trace single-gene disorders?
3) What can make tracing difficult?
1) True
2) Ask about family hx of pt, then summarize in a pedigree if possible
3) Especially early and lethal disease
66
Pedigrees:
1) The affected individual being studied is called what?
2) Who does first degree include?
3) What abt second degree?
1) "Proband”
2) Mom / dad, brother / sister, children
3) Grandma / grandpa, uncle / aunt, nephew / niece, and half-siblings
67
1) What is an example of a third degree relation?
2) When can the term "isolated case" be used?
3) Define "sporadic case"
1) First cousins
2) If it occurs only in the proband
3) If new case is shown to occur due to new mutation
68
Regarding mendelian inheritance, what 2.5 factors matter the most?
1) Is the disease on an autosome or a sex chromosome?
2) Is the disease dominant or recessive?
-Remember, dominant is expressed with just one allele and recessive needs both
½) Were mom and dad homozygotes or heterozygotes?
69
List the 3 general rules for autosomal gene mendelian inheritance
1) Transmission of autosomes is your classic Punnett square transmission
2) A mutant allele in a heterozygous parent has a 50% chance of being passed on to baby
3) Baby’s sex does not matter
70
What are the general rules for X-linked mendelian inheritance?
1) Males give their Y chromosome to all their sons, so they give **no** X-linked genes to male heirs
2) Males give their X chromosome to all their daughters, so they **always** pass X-linked genes to their female heirs
71
What comes exclusively from mom because sperm don’t pass this along?
Mitochondrial DNA
72
When all mom’s babies have the disease, it’s probably ____________________.
Mitochondrial
73
1) Define dominant
2) Define recessive
1) The disease is present if the patient has just one copy of the dominant allele
2) The disease is only present if both the patient’s alleles are present
74
1) When do you see recessive disease?
2) When do you see the dominant gene?
1) Homozygotes, hemizygotes, compound heterozygotes
Never in (regular) heterozygotes!
2) Homozygotes AND heterozygotes
75
A disease demonstrates “incomplete dominance” when ________________ dominant individuals suffer more severely from autosomal dominant disease than their _______________ counterparts
homozygous; heterozygous
76
1) Autosomal recessive inheritance shows up in who?
2) Why?
1) Only in homozygous recessive individuals with two mutant alleles; not heterozygotes
2) Generally, the mutant allele is reducing or eliminating the function of the gene product, often causing loss-of-function
77
Autosomal recessive disorders:
1) The most common type of transmission is from what group?
2) True or false: as long as both mom and dad have the recessive gene somehow, they can make a baby with the recessive phenotype
1) Heterozygous carriers
2) True
78
1) Define consanguinity
2) What does it increase the chance of?
3) What does finding it suggest?
1) Descended from the same ancestor
2) Increases the chance of baby getting mutant allele for obvious reasons
3) Suggests (but does not prove) that a disease may be autosomal recessive
79
1) What is consanguinity more common as? Why?
2) Give an example
1) A factor in very rare disease; bc it is less likely that two random people will carry a rare allele
2) Xeroderma pigmentosum
80
1) What type of mutation is typically seen in in siblings and potential offspring of the proband – not in parents, offspring, or other relatives?
2) Who is typically affected by this type, men or women?
3) Who is an asymptomatic carrier w this mutation type?
4) What is the recurrence risk for each sibling of an affected child?
1) Autosomal recessive
2) Usually, males and females equally affected
3) Parents of affected child
4) About 25%
81
1) Define Sex-influenced Autosomal Recessive (side-note)
2) Give an example
1) Autosomal disease that varies in its **severity** in males and females
2) Hereditary hemochromatosis is autosomal recessive phenotype, causing increased levels of iron, that is 5-10 times more common in males
-Males and females have different penetrance
82
1) Define hemochromatosis
2) What is its penetrance and expressivity?
3) What inheritance pattern does it have?
1) Disease of iron overload resulting in mutation of the HFE gene
2) Incomplete penetrance; variable expressivity
3) Autosomal recessive
83
1) What is the average age of onset of hereditary hemochromatosis?
2) What are the early Sx?
3) What abt the later Sx?
1) 40-60
2) Fatigue, arthralgia, abd pain, impotence / decreased libido
3) Hyperpigmentation (bronzing), DM, cirrhosis, hepatomegaly, cardiomyopathy
84
1) Pt’s with cirrhosis and hemochromatosis have _________% chance of hepatocarcinoma even after treatment.
2) What two lab results would be abnormal if a pt had this?
3) How is it Dxd?
4) How is it treated?
1) 10-30%
2) Elevated serum transferrin iron saturation & elevated serum ferritin
3) Genetic testing
4) Phlebotomy
85
1) Body stores of iron determined by what?
2) What regulates these stores? Where is it made?
3) What does a mutant HFE gene do?
1) Dietary absorption from enterocytes in small intestine, and release of iron from macrophages that phagocytize RBC’s
2) Iron response hormone, **hepcidin**, which is synthesized in the liver and released to block further iron absorption when supplies are good
3) Inhibits hepcidin signaling, disinhibiting enterocytes and macrophages to release iron
86
What are the two types of hereditary hemochromatosis? Specify which makes up most patients.
1) Most patients homozygous for Cys282Tyr (cystine / tyrosine) mutation
2) Compound heterozygous for Cys282Tyr/His63Asp (Histidine / aspartate)
87
Hereditary hemochromatosis:
1) True or false: Homozygosity does not always lead to dz
2) Penetrance is in question and may vary from _________ to _______% depending on how disease is defined.
3) What are 2 ways to define disease?
1) Homozygosity does not always lead to dz
2) Penetrance is in question and may vary from 10% to 70% depending on how disease is defined
3) Organ damage and elevated biomarkers
88
What is the sex difference in penetrance for hemochromatosis?
Females have lower iron intake, lower etoh use, increased iron loss through menstruation, so women usually do not develop sx until after menopause
89
1) Autosomal Dominant Inheritance risk and severity is determined by what?
2) Achondroplasia, as an example, is ________________________, because it is usually fatal when ___________________.
1) Whether trait is pure dominant and by whether one or both parents are affected
2) incompletely dominant, homozygous
90
Autosomal Dominant Inheritance:
1) In what generations does the phenotype usually appear?
2) True or false: Each affected person has an affected parent. Explain your answer and list any exceptions.
3) Any child of affected heterozygous parent has ____% chance of having disease
4) Who are equally likely to give it to children of either sex: males, females, or both?
1) In every generation
2) True; exceptions are due to incomplete penetrance, variable expressivity, and new mutations
3) 50%
4) Males and females equally likely to give it to children of either sex
91
Sex-limited Autosomal Dominant Disease: Male-limited precocious puberty
1) What gene is mutated?
2) What does this mutation do?
3) What are the physical Sx?
1) LCGR gene which encodes receptor for luteinizing hormone
2) Constitutively activate receptors signaling luteinizing hormone even in its absence
3) Affected boys develop secondary sex characteristics with growth spurt at 4 years of age; epiphyseal fusion occurs early and adults have short stature
92
Why do we know that male-limited precocious puberty isn't X-linked?
Because fathers can give it to their sons
93
X & Y chromosomes:
1) Lineage of __ is easy, but there are almost no genes here
2) For sex linked dz then, we look to the ____ chromosome
1) Y
2) X
94
What are the possibilities for males and females for X-linked disease?
1) Male is hemizygous for mutant allele
2) Female is heterozygous with one wild-type dominant allele, homozygous with mutant allele, or a compound heterozygote
95
1) True or false: Genes on X chromosomes are distributed unequally to males and females
2) True or false: X inactivation is normal and ubiquitous in females. Explain your answer.
1) Genes on X chromosomes are distributed unequally to males and females
2) X inactivation is normal and ubiquitous in females; this equalizes gene dose between both human sexes
96
True or false: Two female heterozygotes with the same disease may have very different presentations for this reason because their mosaicism will vary
True
97
1) What two ways can you get hemophilia A?
2) What is the expressivity?
3) What is it linked to?
1) Intrachromosomal recombination and Movable element insertion
2) Variable expressivity
3) X-linked
98
What is hemophilia A (method 1)?
Inversion and mismatched recombination
99
Hemophilia A (Method 2):
1) Estimates are that in any individual ~100 copies of a sublclass of LINE segments are candidates for retrotranscription. What does this do?
2) LINE sequences many kilobp long interrupt the coding sequence for _____ after their insertion into _____ [intron/exon]
1) Generates genetic diversity, but also is one cause for hemophilia through insertional mutagenesis
2) F8; F8 exon
100
Hemophilia A:
1) What's the age at onset?
2) What are its 3 primary symptoms?
1) Infancy to adulthood
2) Bleeding, hemarthroses, hematoma
101
1) True or false: Factors in the clotting cascade are present in circulation at all times, though inactive
2) What do clotting factors do when sequentially activated? Which two in particular amplify this cascade to accomplish this?
3) Deficiency in these two factors can be caused by what two things?
4) What can account for each of these?
1) True
2) Fibrin clot; factors VIII (8) and IX (9)
3) Hemophilia A or B respectively
4) Mutations in F VIII and F IX genes
102
1) How is hemophilia A diagnosed?
2) How is it treated?
1) Identifying low factor VIII in presence of normal von Willebrand factor
2) Factor replacement therapy
103
Hemophilia A:
1) What is its well-defined pattern?
2) Expressed in all __________ who receive it and disease is limited to _____________.
3) Who do those with the disease inherit the disease from?
1) X-linked recessive
2) males; males
3) Either mom or dad
104
True or false: In X-linked disease, male does not give the allele it to all his daughters, and doesn't give it to any of his sons
False; Male gives the allele it to **all** his daughters (though they won’t show the phenotype) and none of his sons
105
X-linked recessive: Affected females occur under what two circumstances? Which is more common?
1) Female could be homozygous for the disease
-very very very unlikely, though
2) Female is a “manifesting heterozygote”
-more commonly
106
1) What could occur under some circumstances of X inactivation?
2) Is this random?
3) What happens if skewed X inactivation occurs?
1) A female could be a “manifesting heterozygote” for hemophilia A
2) Usually
3) The choice of which X to terminate is made early on in development when there is a fewer number of cells, and the presence of the mutant allele may proliferate at a higher rate
107
X-linked dominant:
From an affected male, all of his ___________ would have it, and none of his _____________
daughters; sons
108
1) What rare conditions have odd transmission patterns due to their extreme lethality in males?
2) Why don't boys display this disease?
1) X-linked dominant
2) Their fitness in this disease is zero
109
Give an example of a condition w. X-linked dominant male lethality, and what it looks like in females
Rett syndrome: Normal development in females for 6 months; then speech, coordination, hand movement is lost
110
Give and describe an example of X-linked dominant with Male Sparing (an exception to the rule).
What are the Sx and who is unaffected?
X-inked epilepsy and cognitive impairment:
-Asymptomatic at birth until second year of life
-Seizures, regression of development with mild to severe cognitive dysfunction
-Males are completely unaffected
111
What is one theory regarding X-linked epilepsy and cognitive impairment (an example of male sparing)?
-Females with disease are mosaic for protocadherin 19, a cell surface protein in the brain, due to random X inactivation
-Males have uniform surface protein and no disease
112
X-linked dominant Pointers:
1) Affected males with normal mates have no affected _________ and no normal ____________.
2) Both male and female offspring of female carriers have ____% risk of inheriting the phenotype
Affected females are roughly twice as common as affected males, but they typically have milder expression of the phenotype
1) sons; daughters
2) 50%
113
1) What two things made in a cell have DNA from nucleus?
2) The mitochondrial genome has _____ genes that make _____ subunits of enzymes involved in ___________________________ as well as __________RNAs and _____________RNAs required for making these enzymes
1) RNA and protein
2) 37; 13; oxidative phosphorylation; ribosomal RNAs and transfer RNAs
114
Why are mitochondrial diseases often severe?
Because energy production is so fundamental and ubiquitous to all cellular function
115
X-linked recessive disease:
1) It occurs in ___[boys/girls]_____
2) Male gives the allele it to all his ___________ (though they won’t show the phenotype) and none of his ____________.
3) Put another way, if the patient demonstrates X-linked recessive disease, the patient is ___[male/female]___ and got it from their __[mother/father]__!
1) Boys
2) daughters; sons
3) male; mother!
