Flashcards in Genetic diseases Deck (91):
Mutations of a certain gene _____ may affect one or both of the chromosomes in a pair
_________ refers to a permanent change in the DNA
mutations affecting __________ cells can result in tumors or developmental malformations
what is a Point mutations (missense mutation)? what is an example of a point mutation?
single nucleotide base substituted.
Example: sickle cell anemia
what is a Frameshift mutation?
insertion or deletion of one or two base pairs, altering reading frame of the DNA strand
what occurs during Trinucleotide repeat mutations?
amplification of sequence of 3 nucleotides
what is an example of trinucleotide repeat mutations?
Fragile X syndrome
permanent genetic changes affecting ________ can be inherited
what are the 3 types of mendelian disorders?
Sex-linked (X-linked) Disorders
what are the 2 types of polymorphisms?
Single nucleotide polymorphisms
Copy number variations
a _________ is a variation in just one nucleotide (for example, A or T) at a single site on the DNA molecule
single nucleotide polymorphism
single nucleotide polymorphisms May be markers for multigenic complex diseases, such as _______ or __________
diabetes or hypertension
what are the characteristics of Copy number variation polymorphisms?
- different numbers of large contiguous stretches of DNA, from 1,000 to millions of base pairs
- About half involve gene-coding sequences
______________ changes result in modulation of gene expression without altered DNA sequence
_________ of promoter regions in the DNA makes them inaccessible to RNA polymerase
what type of residues are methylated during epigenetic inactivation?
_______________ inhibit translation of their target messenger RNAs into their corresponding proteins
"functions in RNA silencing and post-transcriptional regulation of gene expression"
Autosomal dominant implies that the altered gene locus is on an _________
during what type of disorder will the disease be evident clinically when only ONE of the chromosomes in the pair exhibits a mutation at the affected gene locus
T/F: The majority of autosomal dominant disorders create outward physical changes
huntington's disease is classified as a ___________ disorder
T/F: Approximately one-quarter of the offspring will have the disease if only one parent is affected with huntington's disease
one half of offspring
what is "reduced or incomplete penetrance"?
Person has a mutant gene but does not express it phenotypically
_____________ means the trait is seen phenotypically in the individuals having the mutant gene but is expressed differently among individuals
how could a child suffer from an autosomal dominant disorder, but their parents are unaffected?
due to "De Novo mutation"
- the parents don't have the autosomal dominant gene because their disease arose from a new mutation
_________ disorders represent the largest group of mendelian disorders
autosomal recessive disorders
T/F: the parents of people suffering from autosomal recessive disorders usually show similar symptoms as their offspring
parents are usually asymptomatic
when are rare autosomal recessive diseases usually seen?
when the affected child (proband) is the product of a consanguineous relationship
what are the characteristics of all autosomal recessive disorders?
• Two germline mutations (one from each parent)
to develop disease
• Equally transmitted by men and women
• 25% of offspring; horizontal pattern in family
Many autosomal recessive disorders present with _______ defects that produce inborn errors of metabolism
_________ individuals of autosomal recessive disorders will often show reduced, but not complete mutation/inactivity, of the normal enzyme
X-linked disorders are also known as "_________" disorders
T/F: although rare, Y-linked genetic disorders do occur
- nobody has ever found a y-linked disorder (thanks dad)
what is the only trait that has been linked to the y-chromosome?
Almost all X-linked disorders are __________ in their inheritance pattern
what inheritance pattern is observed during sex-linked disorders (heterozygosity, homozygosity, et cetera
- women must be homozygous to show disease
- men are heterozygous (mutated X is from the MOTHER)
what occurs during lysonization?
- occurs Sixteen days after conception
- all but ONE X chromosome is randomly inactivated in all of the cells within the zygote
what is Unfavorable lyonization?
refers to inactivation of an abnormally high percentage of normal X chromosomes
the result of ___________ would be the presence of x-linked disorders appearing in heterozygous females
Oral-Facial-Digital syndrome (OFD) type 1 is an example of what type of genetic disease?
Marfan syndrome is a autosomal dominant disorder of _________________
what gene is mutated in Marfan syndrome?
the FBN1 gene
a mutation of the FBN1 gene (marfan syndrome) will result in abnormal formation of what connective tissue protein?
what is the prevalence of marfan syndrome?
1 in 5,000
what are the physical characteristics of someone suffering from Marfan syndrome?
- Tall, thin body habitus with abnormally long legs, arms and fingers
- Dislocation of lens of the eye
- Aortic aneurysm and dissection leading to heart failure
At least ___ different types of ehler-danlos syndrome may exist
what are the characteristics of Ehlers-Danlos syndrome?
Hyperextensible skin and hypermobile joints
Skin fragility and delayed wound healing
Rupture of colon, large arteries
what is the prevalence of Familial Hypercholesterolemia?
1 in 500
Familial Hypercholesterolemia result in the mutation of what type of proteins?
what is the result of Familial Hypercholesterolemia?
- impaired metabolism and increased LDL cholesterol in the plasma
- causes xanthomas of the skin and premature atherosclerosis
what are the effects on cholesterol for heterozygotes and homozygotes during Familial Hypocholesterolemia?
Heterozygotes have 2-3x increased cholesterol levels
homozygotes have over 5x normal levels
what are the 2 diseases caused by Mutations in Structural Proteins?
(which 2 impair normal collagen synthesis/function)
1) Marfan Syndrome
2) Ehlers-Danlos Syndromes
__________________ results from the mutation of a receptor protein
what 2 diseases are caused by by Mutations in genes coding for Enzyme Proteins?
2) Lysosomal Storage Diseases
____________ is an autosomal recessive disorder that affects 1 in 10,000 Caucasian infants
what enzyme is lacking during phenylketonuria? what does this cause?
- phenylalanine hydroxylase
- leads to hyperphenylalaninemia and PKU
elevated phenylalanine will have what effects on infants?
- elevated phenylalanine levels impair brain development
- leads to mental retardation
what are the characteristics of lysosomal storage diseases?
- Autosomal recessive transmission
- Commonly affect infants and young children
- Accumulation of insoluble large molecules (sphingolipids and mucopolysaccharides) in macrophages
what are some examples of lysosomal storage diseases?
Mucopolysaccharidoses (Hurler & hunter disease)
Disorders with Multifactorial Inheritance share what common characteristics?
- Two or more genes responsible, plus environmental, nongenetic influences
- Frequency of inheritance ranges from 2-7%
what causes Mucopolysaccharide storage diseases?
Due to lack of any one of several enzymes necessary to degrade mucopolysaccharides
what are the physical signs of mucopolysaccharide storage diseases?
Affected patients have:
- coarse facial features
- clouding of cornea
- joint stiffness
- mental retardation
________ disease is caused by a deficiency of alpha-L-iduronidase
what therapy can help patients with Hurler disease?
bone marrow transplants
Hunter Syndrome is the result of a deficiency of ___________
(hurler is ALPHA-L-iduronidase)
what is the inheritance pattern of Hunter syndrome?
X-linked inheritance pattern
how does Hunter syndrome differ from Hurler syndrome?
hunter syndrome shows an absence of corneal clouding and milder clinical course
it is estimated that 1 in 200 newborns have a ______________ abnormality
A normal chromosomal count (2 X 23 = 46) is termed _______
An increased chromosome count that is a multiple of that normally seen (i.e. 3 X 23 or 4 X 23) is termed ___________
what happens to most cases of polyploidy?
Any chromosome number that is not an exact multiple of the normal chromosome count is termed _________
_____________ and __________ are both examples of aneuploidy
trisomy (extra chromosome)
monosomy (lacking 1 chromosome)
________________ is the transfer of a part of one chromosome to another nonhomologous chromosome.
__________ is when a chromosome breaks in two points, then the released fragment is reunited after a complete turnaround
what causes down syndrome?
a trisomy (3rd copy) of the 21st chromosome
what factor plays the greatest role in the likelihood of down syndrome?
advanced maternal age
________________ of chromosome 21 during formation of the ovum is the cause of down syndrome
meiotic non-disjunction of chromosome 21
what are the 2 Cytogenetic Disorders Involving Sex Chromosomes?
1) Klinefelter Syndrome
2) Turner Syndrome
***down's syndrome is NOT on the sex chromosome
____________ is Defined as male hypogonadism that develops when there are at least two X chromosomes and one or more Y chromosomes
what causes Turners syndrome?
Due to partial or complete absence of one of the X
what are the symptoms of turners syndrome?
Markedly short stature
webbing of the neck
low posterior hairline
variety of congenital cardiovascular malformations
failure to develop secondary sex characteristics
what techniques can be used to diagnose genetic diseases?
1) Fluorescence in situ Hybridization (FISH)
2) Comparative Genomic Hybridization
3) molecular diagnosis (PCR amplification)
what are the indications for PRENATAL genetic testing?
Mother’s age >34 years
Parent who is a carrier of a chromosomal translocation
Hx of a previous child with chromosomal abnormality
Parent who is a carrier of an X-linked disorder
what are the indications for POSTNATAL genetic testing?
Multiple congenital anomalies
Unexplained mental retardation and/or developmental delay
Suspected aneuploidy (e.g., Down syndrome)
Suspected sex chromosomal abnormality
Multiple spontaneous abortions
what is an autosomal dominant disease that has nearly 100% penetrance, but has extreme variability in its expression?
"Hemophilia A" is an example of what class of inherited disorder?
what genetic disorder will commonly cause an enlarged tongue?
_______________ (a sex chromosome disorder) will increased the frequency of taurodontism
most people with ________________ will have a genotype of 47,XXY