Polymorphism
Multiple forms (alleles) of a gene in population (>1% of population).
Homozygote
Possess the same alleles at a locus
Heterozygote
Possess different alleles at a locus
Locus
Location of gene on chromosome
Dominant
Require only one copy of the mutation to produce disease
Recessive
Requires two copies of the mutation to produce disease
Recurrence risk
Probability that the offspring of a couple will express the genetic disease.
For single gene disorders, it does not depend on the number of previously affected/unaffected offspring. Depends on mode of inheritance of a disease.
Consultand
The person who approaches a physician or
geneticist for a consultation.
- this person may, or may not, be affected.
Proband
The affected individual in the family who gains
the attention of the physician due to a genetic condition.
Consanguinity
Medical term for "in-breeding." Sexual relationship or marriage between second cousins or closer than second cousins.
Explain what are identical twins known as monozygotic twins?
Arise as result of fertilization
of a single zygote. Possess
identical genes
Explain what are identical twins known as dizygotic twins?
Arise as result of fertilization
of two ova. Genetically share
about 50% genes (Sibling)
What are the two different ways of indicating carrier individuals in a pedigree diagram?
1) Half filled symbols
may be used to
indicate carriers.
2) A dot may also be used to indicate carrier status.
What are the two major categories of Modes of Inheritance?
Mendelian Mode of Inheritance and Non-Mendelian (or also known as Mitochondrial Mode of Inheritance).
What are the two major types of Mendelian Modes of Inheritance?
What are the 5 different types of Mendelian Modes of Inheritance?
Autosomal (involving the 22 pairs of autosomal chromosomes) and Sex chromosomal (involving the 23rd pair of sex chromosome).
Autosomal:
1) Autosomal Dominant
2) Autosomal Recessive
Sex chromosomal:
3) X-linked Dominant
4) X-linked Recessive
5) Y-linked in
What is a Mitochondrial mode of inheritance?
Disease due to a mutation in a gene encoded by mitochondrial DNA.
What is the difference between locus and allele?
Locus is the location of the gene on a chromosome, whereas allele is the different versions of the same gene at occurs AT A SPECIFIC LOCUS on a chromosome.
What should you assume about the mode of inheritance of Autosomal Dominant disorders?
Always assume that autosomal dominant disorders are in the heretozygote state, unless otherwise specified; because they can "rarely" be presented in the homozygous state as well.
KEY FACT / ASSUMPTION:
Autosomal dominant disorders manifest in the heterozy
What is vertical inheritance?
Which type of mode of inheritance disorders exhibit vertical inheritance?
In vertical inheritance, affected children receive the disease causing gene from an affected parent. IN OTHER WORDS, the disease does not SKIP generations!
Autosomal Dominant Disorders exhibit vertical inheritance (no skipping of generations because every
Autosomal Dominant disorders have
1) what type of mode of inheritance?
2) do diseases skip generations?
3) do such diseases affect males and females equally?
4) do such diseases have male to male transmission?
5) do such diseases have affected parents aff
Autosomal Dominant disorders have
1) what type of mode of inheritance? VERTICAL
2) do such diseases skip generations? NO
3) do such diseases affect males and females equally? YES
4) do such diseases have male to male transmission? YESSS
5) do such disease
True or False: All Dominant disorders (whether autosomal dominant or X-linked dominant) do NOT skip generations.
True! No skipping of generations is a key stone feature of dominant disorders!
How can you tell the difference between X-linked dominant and Autosomal dominant disorders (considering that both have no skipping of generations / vertical inheritance)?
Autosomal dominant disorders characteristically exhibit FATHER TO SON transmission; whereas X-linked dominant disordres characteristically DO NOT exhibit father to son transmission.
True or False: The sex/gender of the parent is not important in autosomal dominant disorders.
TRUE!
What is the Recurrence Risk for Autosomal Dominant Inheritance?
Since in autosomal dominant disorder only one mutant allele is sufficient to cause the disease phenotype in affected individuals; capital A represents the disease allele and lower-case 'a' represents normal allele. A punnet square between Aa (affected par
Charcot-Marie-Tooth (CMT) Neuropathy
Pronounced Shahrr-co Mahree Tooth disease or Shahrr-co Mahree Tooth Neuropathy.
CMT is a group of genetically inherited disorders of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts
What is the MODE OF INHERITANCE for familial hypercholesterolemia disorder?
Autosomal Dominant
If it is known that a particular disorder has an autosomal dominant mode of inheritance and only one parent is affected (i.e. has the disease) then what is the probability that a couple's next child will be affected?
For that same couple, what is the prob
ALL autosomal dominant disorders ALWAYS have 50% recurrence risk (regardless of the sex/gender of the parents as well as regardless of the sex/gender of the kids)!
For that same couple, the probability for the second pregnancy / child stays the same as th
If it is known that a particular disorder has an autosomal dominant mode of inheritance and BOTH parents are affected (i.e. have the disease) then what is the probability that a couple's next child will be affected?
For that same couple, what is the proba
What is the MODE OF INHERITANCE for LDL receptor
deficiency disorder?
LDL receptor deficiency is the same as familial hypercholesterolemia disorder!
Mode of Inheritance is Autosomal Dominant.
Details about Familial Hypercholesterolemia:
Patients have high levels of LDL with normal VLDL.
The heterozygous form occurs in a lot
What is the MODE OF INHERITANCE for Huntington's disease?
Huntington's disease has autosomal dominant inheritance, meaning that an affected individual typically inherits one copy of the gene with an expanded trinucleotide repeat (the mutant allele) from an affected parent.
Huntington's disease (HD) is a neurodeg
What is the MODE OF INHERITANCE for Myotonic dystrophy disease?
The disease display an autosomal dominant pattern of inheritance.
Myotonic dystrophy (dystrophia myotonica, myotonia atrophica) is a chronic, slowly progressing, highly variable, inherited multisystemic disease.
It is characterized by wasting of the muscl
What are 2 examples of triplet repeat expansion
disorders?
Myotonic dystrophy and Huntington's disease are examples of triplet repeat expansion disorders, both of which have autosomal dominant mode of inheritance.
What is the MODE OF INHERITANCE for Marfan syndrome?
Have autosomal dominant mode of inheritance.
What is the MODE OF INHERITANCE for Osteogenesis imperfecta?
Have autosomal dominant mode of inheritance.
What is the MODE OF INHERITANCE for Achondroplasia?
Have autosomal dominant mode of inheritance.
Achondroplasia
� FGFR3 mutations
� FGFR3 codes for a transmembrane receptor that is involved in differentiation of cartilage to bone
� Mutations in FGFR3 result in severe stunting of growth
What is the MODE OF INHERITANCE for Neurofibromatosis type I disease?
Have autosomal dominant mode of inheritance.
� Mutations in neurofibromin (NF1) gene.
� NF-1 is caused by different mutations in the NF-1 gene
(allelic heterogeneity = different mutations of the same gene resulting in the same phenotype (condition/disease
What is meant by variable expressivity?
When not all patients with the disease have the same severity of the symptoms then that disease is said to exhibit variable expressivity.
What is allelic heterogeneity?
Different mutations of the same gene resulting in the same phenotype (i.e. condition or disease) is called allelic heterogeneity.
What is the MODE OF INHERITANCE for Acute intermittent porphyria?
Have autosomal dominant mode of inheritance.
What is your mnemonic for all the autosomal dominant diseases/disorders/syndromes that you have to know for SGU Genetics course?
Possible mnemonic for all the autosomal dominant diseases' mode of inheritance is: F! HAM MOAN!!
F = familial hypercholesterolemia / LDL receptor def.
H = Huntington disease
A = Anchondroplasia
M = Myotonic dystrophy
M = Marfan syndrome
O = Osteogenesis i
When a disease is pleiotropic disease; what does this describe about how the disease manifests itself in patients?
It means that the disease affects more than one organ system even though there is a mutation of a SINGLE gene that is causing the disease.
Why do autosomal dominant mutations manifest in the
heterozygous state?? Give three reasons!!!
1) Loss-of-function mutations (Haplo-insufficiency): in which half normal levels of the gene product result in phenotypic effects.
2) Gain-of-function mutations: result from increased levels of gene expression or the development of a new function of the g
What are two conditions / diseases that are examples of GAIN OF FUNCTION MUTATION?
Examples include Huntington disease and achondroplasia
What are three conditions / diseases that are examples of LOSS OF FUNCTION MUTATION (aka Haplo-insufficiency)?
- Examples include cell membrane receptors (familial hypercholesterolemia)
- AIP (enzyme deficiency, heme can't be produced fast enough)
- Consider OI type I
What are two conditions / diseases that are examples of DOMINANT NEGATIVE MUTATION?
Examples include collagenopathies such as OI Type II, III, or IV also Marfan syndrome (defect in fibrillin).
True or False: In all known cases a person who is homozygous for alleles causing autosomal dominant (AD) disease - the prognosis is worse.
Yes! This can be seen in Familial Hypercholesterolemia, Achondroplasia, and Huntington disease.
However, note that in all of the autosomal dominant diseases, a patient who is homozygous for disease alleles (for an AD disorder) is EXTREMELY rare!!!
Therefo
True or False: All humans carry recessive mutations.
True! It is predicted that each of us have 7 to 10 recessive mutations; only when we mate with someone else with the same mutations will we find out that we are carrier of a disease.
True or False: Autosomal recessive disorders are expressed in the homozygous state, whereas autosomal dominant disorders are expressed in the heterozygous state.
True. Generally, both parents are carriers of a
disease causing mutant allele. Carriers are phenotypically
normal - all humans carry recessive mutations
What is horizontal inheritance?
When a disease in a family is seen in only one generation of a pedigree then it is said that the disease exhibits horizontal inheritance!
True or False: Vertical inheritance is exhibited in ALL autosomal recessive disorders, whereas Horizontal inheritance is exhibited in ALL autosomal dominant disorders.
FALSE. It is in fact that horizontal inheritance that is witnessed in ALL autosomal recessive disorders, whereas vertical inheritance (no skipping of generations) is witnessed in ALL autosomal dominant disorders.
To recap:
HORIZONTAL inheritance = autosom
What is a common feature of both the autosomal dominant and autosomal recessive disorders?
Both, autosomal dominant and autosomal recessive disorders, affect males and females equally.
What is are different features between autosomal dominant and autosomal recessive disorders?
Autosomal Dominant Mode of Inheritance:
1) Father to son transmission is seen.
2) No generations are skipped (more than one generation has the condition on the pedigree); vertical inheritance.
3) Only one mutant allele is needed for the disease phenotype
Describe autosomal recessive disorders?
� Autosomal recessive diseases are usually seen in only one
generation of a pedigree (horizontal inheritance)
� Autosomal recessive diseases are expressed only in the
homozygous state. Parents are usually carriers of the disease
causing allele. Siblings a
True or False: Siblings are more commonly affected in autosomal recessive disorders.
True.
Recurrence Risk for Autosomal Recessive Inheritance with a carrier mother and a carrier father?
In autosomal recessive disorders
A = normal allele
a = disease allele
aa = affected individual
Aa = carrier individual
AA = normal individual
This is different from autosomal dominant disorders:
A = disease allele
a = normal allele
Aa = affected individua
True or False: Autosomal recessive diseases are expressed only in "homozygous" state; this is unlike autosomal dominant disease which are only expressed in "heterozygous" state.
True.
Autosomal recessive diseases are usually seen in only one
generation of a pedigree (horizontal inheritance).
Autosomal recessive diseases are expressed only in the
homozygous state.
Parents are usually carriers of the disease
causing allele.
Sibling
What is the probability that a couple who are both carriers for an autosomal recessive disorder is a carrier of the recessive allele?
CAUTION. If the child is going to be a carrier then it cannot be 'aa' or be affected. I know that all autosomal recessive disorders produce 25% homozygous affected, 75% phenotypically normal, 50% carriers, and 25% homozygeous normal. However, this questio
What is the MODE OF INHERITANCE for
� Cystic fibrosis
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Sickle cell anemia
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Phenylketonuria
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Tay-Sachs disease (Hexosaminidase A deficiency)
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Congenital deafness (autosomal recessive)
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Hemochromatosis (delayed age of onset)
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Alkaptonuria (delayed age of onset)
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Homocystinuria
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� Galactosemia
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What is the MODE OF INHERITANCE for
� SCID due to adenosine deaminase deficiency
- Severe combined immune deficiency
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
Autosomal recessive SCIDS is due to ADA (adenosine deaminase) enzyme deficiency; when AD
What is the MODE OF INHERITANCE for
� Most enzyme deficiencies
- Beware those that are X-linked, and IAP
Autosomal Recessive Disease/Disorder (this is expressed only in a homologous state--when there are two mutant copies of the same gene, one from mom and one from dad).
What are the two types of loss of function mutations?
1) Hypomorph and 2) Amorph
Hypomorph loss of function mutation is when there is reduced activity of a gene.
Amorph loss of function mutation is when there is complete loss of gene product.
What are the FOUR diseases/disorders/conditions that we learned in our genetics course which exhibit "Allelic Heterogeneity"?
Neurofibromatosis-1
Hemochromatosis
Hemophilia A
Cystic Fibrosis
1) NF-1 is caused by different mutations in the NF-1 gene.
2) Hemochromatosis can either have mutations in the HFE gene at two different locations (C282Y versus H63D loci of the same gene) w
Autosomal recessive SCIDS is due to which enzyme's deficiency?
ADA = adenosine deaminase
What does "having the same mutant allele" imply?
When the parent is a carrier then "having the same mutant allele" means that you're finding the probability of the kids also being carriers, etc.
How do you find the probability of the grandchildren?
Simply multiply the two probabilities with each other. (1/2 x 1/2 = 1/4 or 25%)
What is a Pseudo-Autosomal Dominant disease or disorder or condition?
Is actually an Autosomal Recessive disorder/disease but it appears like an autosomal dominant disease on the pedigree.
How is pseudo-autosomal dominant mode of inheritance (which is actually autosomal recessive mode of inheritance) different from the actual autosomal dominant mode of inheritance?
How do we know that a pseudo-autosomal dominant is in fact an autosomal rece
Pseudo-autosomal dominant is BEHAVES LIKE the autosomal dominant in that it:
1) presents in two or more generations in a pedigree vertically
2) an affected parent may have an affected child
3) This is also known simply as "PSEUDO-DOMINANCE of an autosomal
What are the two common explanations for why we observe pseudo-autosomal dominant disorder?
We should not NEVER assume based only on the pedigree that a disease that looks like an autosomal dominant is an pseudo-autosomal dominant UNLESS we are told by the question stem that there is
1. High carrier frequency of the disorder
- sickle cell anemia
Define "pseudo dominant" mode of inheritance?
Apparent Autosomal Dominant inheritance when a
heterozygote & homozygote for an autosomal recessive disorder have affected children.
How many blood type groups are there?
4 (or 8 if you count the +/- factor)
A type
B type
O type
AB type
In which mode of inheritance does the blood type get transmitted?
Co-dominance
What is Pseudoautosomal region?
Region of chromosomes that match. It is necessary to line up chromosomes correctly during meiosis recombination.
Tell me about X-linked recessive disorders?
X linked disorders are diseases caused by mutations on the sex chromosome called X. Males have XY sex chromosomes, whereas females have XX.
Females (XX)
1) one X having the mutation WILL NOT affect them
2) two Xs having the mutation is VERY RARE but will
Why are males said to be "hemizygous" and not females?
A chromosome in a diploid organism is hemizygous when only one copy is present. Only males have one copy of the X chromosome; every chromosome females have, they also have a copy of it.
Because it refers to the X chromosome; and since males only have half
What is skewed X - inactivation (asymmetric X inactivation) ?
If this asymmetric X-chromosome inactivation occurs, the
carrier may have gene expression activity level that is BELOW NORMAL and thus will experience gene-mutation/disease-like problems.
There is BELOW NORMAL gene expression activity in individual with s
What is the the phenomenon of incomplete or reduced penetrance?
This phenomenon usually / commonly occurs with "autosomal dominant" mode of inheritance.
This happens when the pedigree fits the description of the autosomal dominant inheritance except for an individual who most probably has the disease genotype but does
What affects the penetrance (ability of the disease to actually fully express the manifestations of the disease) of a disease?
Penetrance may be dependent on AGE!!!
---> Especially in adult onset diseases like Huntington disease.
It is important to be able to calculate the recurrence risk given the penetrance of a disease.
If the penetrance of an autosomal dominant disease is
80%, then the recurrence risk for the couple would be?
Because every child with autosomal dominant has 50% chance of being affected and there is a given 80% penetrance then:
50%x80%
----------- = 40% is the answer.
100%
Hemochromatosis is autosomal recessive disorder AND YET it is found to be more severe in males than females; why is that?
Autosomal recessive disorders affect males and females EQUALLY; however sometimes certain disorders can be "variable expression." Variable expression means that two individuals who have inherited the same mutant allele can have different severity due to t
Xeroderma pigmentosum is autosomal recessive disorder AND has variable expression; what increases the risk of developing Xeroderma pigmentosum?
Xeroderma pigmentosum is more severe in individuals exposed more frequently to environmental UV radiation.
What is Pleiotropy?
Pleiotropy is when "a disease causing mutation affects multiple organ systems.
What are two example diseases which exhibit a pleiotropic nature?
Pleiotropy is when "a disease causing mutation affects multiple organ systems."
Two pleiotropic diseases are:
1) Marfan syndrome (mutation in fibrillin gene)
2) Osteogenesis imperfecta (mutation in collagen gene)
1) The disease causing mutation in Marfan
What is locus heterogeneity?
Locus heterogeneity refers to mutations at different loci that cause the same disease phenotype. Many loci can cause the same disease.
What are 7 examples of diseases that demonstrate locus heterogeneity?
1) Osteogenesis imperfecta: Defect in collagen
- Mutations of chromosome 17 (COL1A1 gene) or
chromosome 7 (COL1A2 gene)- lead to the disease
manifestations (phenotype) of osteogenesis imperfecta
� Other disorders that demonstrate locus
heterogeneity:
2)-
What is the more common classic examples of diseases that demonstrate locus heterogeneity?
1) Osteogenesis imperfecta (collagen gene: chromosome 17's COL1A1 gene and chromosome 7's COL1A2 gene)
2) Charcot Marie Tooth disease (AD, AR, or X-linked)
3) BREAST CANCER: BRCA1 locus or BRCA2 locus (on same gene)
4) Congenital Deafness has 15 different
What is Allelic heterogeneity?
Allelic heterogeneity is when DIFFERENT mutations at the SAME locus cause the SAME disease phenotype! In other words, different mutations at the same locus cause the disease.
What is the difference between locus heterogeneity versus allelic heterogeneity?
Locus heterogeneity is when 2 or more DIFFERENT loci (aka 2 or more different genes may be mutated here) mutations cause the SAME disease phenotype, whereas allelic heterogeneity is when 2 or more mutations at the SAME locus (aka in the SAME gene) cause t
What is a compound heterozygote?
This term only refers to allelic heterogeneity demonstrating disorders such as cystic fibrosis, hemochromatosis, or neurofibromatosis.
A compound heterozygote is the affected child who inherits BOTH the paternal as well as the maternal mutations; such an
What is the concept of Germline mosaicism?
� A normal father had two infants affected with
osteogenesis imperfecta with different partners.
The father also has another child that is normal.
The results of the genetic tests for osteogenesis
imperfecta are normal in all the parents.
� This may be du
What are the two key/prominent features/symptoms of Huntington disease (autosomal dominant)?
1) Progressive dementia,
2) Loss of motor control
Delayed age of onset has to be kept in mind when
reading the pedigrees for which disorders?
Huntington disease
Hemochromatosis
Familial breast cancer
Mitochondrial Inheritance
� Mitochondria are inherited
from the mother
� All offspring of an affected
female are affected
� Only females transmit
disease
� Affected father does not
transmit the disease to
children
� BOTH male and female
children of an affected
female are AFFECTED
What is heteroplasmy?
The variable expression / severity of mitochondrial diseases is due to the phenomena of heteroplasmy.
The term heteroplasmy is ONLY associated with mitochondrial diseases!
Some mitochondrias carry disease and some do not... Therefore, the severity of the
What does the mito disease MELAS stand for?
Mitochondrial
Encephalomyopathy,
Lactic
Acidosis, &
Stroke-like episodes
What does the mito disease MERRF stand for?
Myoclonic
Epilepsy w/
Ragged
Red muscle
Fibres
what happens in the mito disease called Leber hereditary optic neuropathy?
Manifests as progressive blindness around 20-30 years of age.
Blindness and cardiac conduction defects are present.
Give an example of digenic disorder and explain this mode of inheritance!
Digenic disorders are newly recognized and were first noted in retinitis pigmentosa in children of parents who each carried a mutation in different RP-associated genes. Both parents had normal vision. With digenic inheritance, normal parents, one of whom
What are the mode of inheritance of Prader Willi syndrome and Angelman syndrome?
Imprinting.
What are the symptoms of Retinitis pigmentosa?
Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment and often blindness. The progress of RP is not consistent. Some people will exhibit symptoms from infancy, others may not notice symptoms until later
Imprinting
� Some genes are active ONLY when transmitted by mother or father.
� For some genes, the maternal loci are active
� And for some genes, the paternal loci are active
What are the two causes of Prader Willi Syndrome (major and minor)? Which diagnostic test can detect it either of these?
1) Prader Willi Syndrome DUE TO a "microdeletion of father's (paternal) chromosome," which causes absence of SNRPN.
2) Prader Willi Syndrome DUE TO a condition known as "uniparental disomy" in which the child has two of mother's (maternal) chromosomes 15
How is detection by FISH molecular diagnostic test done and for what purpose?
Detection by FISH is done by using specific probes against the region of interest.
Remember FISH is used whenever you are FISHing for a specific region to see if it is present or not within the chromosomes of the individual (whole genome).
Give an explanation for the uniparental disomy observed in Prader Willi Syndrome!
Uniparental disomy of Prader Willi syndrome is simply the condition in which the child has two copies of the chromosome 15 (both from the mother and no copy at all from the father of chromosome 15).
A good explanation for why this phenomenon of uniparenta
What is the difference between Angelmann Syndrome and Prader Willi Syndrome?
They both involve chromosome 15th; however these two diseases are quite different in their manifestations/symptoms (i.e. eating too much versus smiling too much).
Trisomy rescue is involved in both conditions.
Angelmann syndrome happens if there were thre
What abnormal event during cell cycle takes place when Prader Willi syndrome is caused by uniparental disomy?
Meiotic I nondisjunction causes uniparental disomy (aka two maternal copies of the chromosome 15 are in the child because when these chromosomes were "homologous chromosomes" during metaphase of meiosis I they failed to separate!
What is another name for the happy puppet syndrome?
Angelmann Syndrome
What are the four triplet repeat disorders?
Hunt My Fragile Friedrich" mnemonic.
Huntington disease (CAG)
Myotonic dystrophy (CTG)
Fragile X syndrome (CGG)
Friedrich ataxia (GAA)
All of these are caused by expansion of triplet repeats!
Repeats are unstable, and repeat size of influences disease
se
Explain the phenomena called "anticipation" and which disorders demonstrates it?
The four triplet repeat disorders (Huntington diease, Myotonic dystrophy, Fragile X syndrome, and Friedrich ataxia) all demonstrate anticipation.
Triplet repeat size influences disease severity; individuals in the recent (newer) generations of a pedigree
What does the codon CAG encode for? Why is it clinically relevant to know about this codon?
CAG encodes for "glutamine."
An expansion of triplet repeats (of above 40 repeats) is said to put an individual at direct risk of developing Huntington disease later on in life (and the higher the number of triplet repeats the sooner the age of onset ther
What are the FOUR locations where the triplet repeats can pop up?
1) At the promoter.
2) In an intron (which is NOT part of the encoded DNA and is excised OUT).
3) In the actual coding region of the gene itself
4) At the 3' end of the gene
If there was an expansion of triplet repeats "at the promoter" then which SPECIFIC disorder that we learned about would be caused?
We only learned about one example of a triplet repeat disorder that occurs AT THE PROMOTER and that is the Fragile X syndrome! See Slide 129/140.
Note: this results in reduced expression of the gene.
If there was an expansion of triplet repeats "in an intron" then which SPECIFIC disorder that we learned about would be caused?
We only learned about one example of a triplet repeat disorder that occurs IN AN INTRON and that is the Friedrich ataxia! See Slide 129/140.
Note: this results in formation of heterochromatin.
If there was an expansion of triplet repeats "in the coding region of the gene" then which SPECIFIC disorder that we learned about would be caused?
We only learned about one example of a triplet repeat disorder that occurs IN THE CODING REGION OF THE GENE and that is the Huntington disease with its CAG repeats increased (which code for glutamine--so there is polyglutamine expansion)! See Slide 129/14
If there was an expansion of triplet repeats "at the 3' end (3' UTR) of the gene" then which SPECIFIC disorder that we learned about would be caused?
We only learned about one example of a triplet repeat disorder that occurs AT THE 3' END OF THE GENE and that is the myotonic dystrophy disease.
--See Slide 129/140.
If there is a mutation that causes polyglutamine expansion; then which disease / disorder does this point to?
Huntington disease!
Fragile X syndrome
� General Info?
� Symptoms?
� Diagnostic Test?
� General Info
1) Triplet repeat expansion (CGG repeat) on the X chromosome.
2) Results in increased methylation of this region and silencing of the FMR1 gene.
3) Females are less severely affected than males.
4) Shows anticipation in successive generatio
A study of the CFTR mutation in two separate families,
revealed a codon deletion in one family and a missense
mutation in the second family. A marriage occurred
between members of these two families, and a child was
born with CF. Which term describes this
Compound heterozygote
Incomplete penetrance
This phenomenon usually / commonly occurs with "autosomal dominant" mode of inheritance.
This happens when the pedigree fits the description of the autosomal dominant inheritance except for an individual who most probably has the disease genotype but does
Locus heterogeneity
Locus heterogeneity refers to mutations at different loci that cause the same disease phenotype. Many loci can cause the same disease.
1) Osteogenesis imperfecta (collagen gene: chromosome 17's COL1A1 gene and chromosome 7's COL1A2 gene)
2) Charcot Marie
Allelic Heterogeneity
Allelic heterogeneity is when DIFFERENT mutations at the SAME locus cause the SAME disease phenotype! In other words, different mutations at the same locus cause the disease.
Locus heterogeneity is when 2 or more DIFFERENT loci (aka 2 or more different ge
A study of the CFTR mutation in two separate
families, revealed a codon deletion in one family and
a missense mutation in the second family. This
illustrates the concept of
Allelic heterogeneity
Anticipation
The four triplet repeat disorders (Huntington diease, Myotonic dystrophy, Fragile X syndrome, and Friedrich ataxia) all demonstrate anticipation.
Triplet repeat size influences disease severity; individuals in the recent (newer) generations of a pedigree
Digenic inheritance
Digenic disorders are newly recognized and were first noted in retinitis pigmentosa in children of parents who each carried a mutation in different RP-associated genes. Both parents had normal vision. With digenic inheritance, normal parents, one of whom
Compound heterozygote
This term only refers to allelic heterogeneity demonstrating disorders such as cystic fibrosis, hemochromatosis, or neurofibromatosis.
A compound heterozygote is the affected child who inherits BOTH the paternal as well as the maternal mutations; such an
Pleiotropic effect
Pleiotropy is when "a disease causing mutation affects multiple organ systems."
Two pleiotropic diseases are:
1) Marfan syndrome (mutation in fibrillin gene)
2) Osteogenesis imperfecta (mutation in collagen gene)
1) The disease causing mutation in Marfan
Heteroplasmy
The variable expression / severity of mitochondrial diseases is due to the phenomena of heteroplasmy.
The term heteroplasmy is ONLY associated with mitochondrial diseases!
Some mitochondrias carry disease and some do not... Therefore, the severity of the
Two individuals who each have the same adult-onset autosomal dominantly inherited disorder meet, fall in love, and have children. Their first-born child inherits the disease allele from both parents. What can be expected in this child?
The disease phenotype is likely to be more severe in the child. It is NOT necessarily true that the child will die in utero (embryonic or perinatal lethality).
Mutation of the splice acceptor site of exon or intron would would the mature mRNA transcript to be what?
LONGER?
or
SHORTER?
And yes donor and acceptor sites DO exist in both exon and introns (though they are commonly referred to as being in the introns
SHORTER.
Mutation of the splice DONOR site of exon or intron would would the mature mRNA transcript to be what?
LONGER?
or
SHORTER?
And yes donor and acceptor sites DO exist in both exon and introns (though they are commonly referred to as being in the introns bec
LONGER.
Helene is a carrier for Duchenne muscular dystrophy. She marries Gary, who has Becker muscular
dystrophy. Helene has just given birth to a daughter. What is the probability that this child will be
affected with a disease associated with a defect of the dy
25% or 1/4