Flashcards in Genetic Diseases Deck (125):
There are ____ pair of autosomes and ____ pair of sex chromosomes.
How many protein-coding genes are there in the human genome (roughly)?
True or False: Alterations in the genetic code results in mutation.
Where do genes reside?
Where are chromosomes?
in the nucleus of the cell
What are the four letters of genetic code?
A, C, G, and T
(adenine, cytosine, guanine, thymine)
Each gene contains the genetic information required to produce ______.
True or False: Mutations of a certain gene locus will only affect one chromosome of the pair.
False: could affect one OR both
When one chromosome of the pair is affected, the individual is ______ for the disorder.
If both chromosomes at a given gene locus are affected, the individual is _______.
Neoplasms affect _____ cells; whereas, inherited conditions affect ______ cells.
What is a point mutation?
also known as "Missense"
a single base substitution (such as in Sickle Cell Anemia)
What is a frameshift mutation?
an insertion OR deletion of 1 or 2 base pairs that results in alteration of the reading frame of the DNA strand (typically results in early stoppage)
What is a "trinucleotide repeat" mutation?
amplification of a 3-nucleotide sequence (ex: Fragile X Syndrome)
____________: variation in just one nucleotide (for example A or T) at a single site on the DNA molecule.
Single Nucleotide POLYMORPHISM
Over 6 million polymorphisms have been identified, but most are within _____, _______, or intergenic regions.
Polymorphisms may be markers for multigenic diseases such as ______ or hypertension.
What are the two types of polymorphisms?
1. single nucleotide
2. copy number variations
What are copy number variations?
different number of large contiguous stretches of DNA (anywhere from 100 to millions of base pairs)
About how many "copy number variations" involve gene coding sequences that may result in phenotypic variation?
________: modulation of gene expression without altered DNA sequence.
True or False: Epigenetic changes will disrupt homeostasis.
False: Epigenetic changes are important in development and in normal homeostasis
Methylation of the promoter region makes it inaccessible to _______ and thus reduces protein synthesis.
What do MicroRNA do?
inhibit translation of their target messenger RNA and thus control or block transcription of the protein
(aka: strands of RNA that DO NOT code for anything themselves but regulate transcription of other proteins....gene silencing)
What are the three types of Mendelian Disorders (diseases caused by single-gene defects)?
1. Autosomal Dominant
2. Autosomal Recessive
3. Sex-Linked Disorders
What are polygenic disorders?
disorders with multifactorial inheritance
What are cytogenetic disorders?
chromosomal aberrations (autosomes, sex chromosomes)
True or False: The production of an abnormal protein can alter phenotype.
What is an autosomal dominant disorder?
the altered gene is on an autosome and the disease will be clinically evident when only one of the chromosomes in the pair is affected at a particular gene locus
Autosomal Dominant disorders present with _________ changes and may exhibit a(n) _______ age of onset.
outward physical changes
delayed age of onset (ex. Huntington's Disease)
With AD disorders, are one or both parents usually affected?
True or False: With AD disorders, only males can have the disorder and transmit the mutated gene.
False: BOTH males and females can have the disorder and transmit the mutation
If only one parent is affected with an AD disorder, what percentage of the offspring will have the disease?
What is "reduced or incomplete penetrance"?
person has a mutant gene but DOESN'T or only PARTIALLY expresses it phenotypically
What is "variable expressivity"?
trait is seen phenotypically in all individuals having the mutant gene but is EXPRESSED differently among individuals
What is "de novo mutation"?
affected individuals may not have affected parents because their disease arose from a NEW mutation
What is an example of an A.D. disease with nearly 100% penetrance?
True or False: 100% penetrance means that everyone who has the mutation will show evidence of the condition and express it fully.
True/False: Everyone WILL show evidence of the condition but the EXPRESSIVITY will be highly variable
What is "Autosomal Recessive Disorder"?
the trait is expressed only if BOTH genes at the given locus are affected (ie: homozygous for the defect)
True or False: A.R. disorders are the most common of Mendelian disorders.
True or False: One parent of an affected individual with an A.R disorder will show the disease.
False: Neither parent will appear affected
What is the chance that heterozygous parents for an AR disorder will have offspring with the disorder? What is the chance that the offspring will be a carrier?.
disease: 25% chance
carrier: 50% chance
What does this statement mean: "the recessive gene is rare in the population, the disorder may be a result of consanguinity"?
there is a horizontal pattern within families, the disorder will most likely be passed among family members of similar genetic backgrounds
Many AR disorders are ______ defects.
For AR disorders, the age of onset is ____ and ______ penetrance is common.
(**AD disorders have late onset and variable penetrance)
On which chromosome are x-linked disorders?
sex chromosome (all sex-linked diseases are on the x chromosome)
True or False: The Y chromosome only carries one significant gene.
True, the SRY gene....sex-determining region
What is the one trait that may be linked to the Y chromosome?
Most sex-linked disorders are ______.
Why are females usually unaffected by sex-linked disorders?
females are XX and these disorders are usually recessive which means they would have to inherit two mutated copies, males are XY (hemizygous) and will express a disease when they inherit one defective X
What is an important X-linked disorder?
What is lyonization?
sixteen days after conception, about 75% of one x-chromosome (maternal or paternal) is randomly inactivated in all of the cells within the zygote
What is unfavorable lyonization?
inactivation of an abnormally high percentage of normal x chromosomes, leading to clinical evidence of a recessive disease in a heterozygous female (i.e.: x-linked)
What is formed from the x-chromosome that is randomly inactivated in the female zygote?
Mutations in Structural Proteins cause mutations in genes that encode proteins necessary for formation of normal ____ and ______.
Marfan Syndrome is an _____ ______ disorder of connective tissue due to mutation of the _______ gene.
Mutation of the FBN1 gene, Marfan Syndrome, results in abnormal ________.
fibrillin (a glycoprotein necessary for normal elastic fiber production)
What are the physical traits of Marfan Syndrome?
tall, thin body habitus
abnormally long legs, arms and fingers (arachnodactyly)
dislocation of the lens of the eyes
aortic aneurysm and dissection leading to heart failure and aortic rupture
(Abe Lincoln! Sudden death of bball players!)
There are at least ____ clinical variants of Ehlers-Danlos syndrome.
six (dominant and recessive)
Why are there different variants of Ehlers-Danlos?
the disease is a result of defective collagen synthesis...there are about 30 different types of collagen and variable tissue distribution
What are the clinical traits associated with Ehlers-Danlos?
Hyperextensible (stretchy) skin
Poor wound healing
What are two diseases caused by mutations in Receptor Proteins?
2. Cystic Fibrosis
True or False: Hypercholesterolemia is one of the more commonly inherited disorders.
True (1 in 500 in the population)
Which gene is mutated in Hypercholesterolemia?
the gene that encodes for the LDL receptor (results in impaired metabolism and increased LDL cholesterol in the plasma)
What would be the result of a mutated LDL receptor?
xanthomas of the skin
True or False: Homozygotes of Familial Hypercholesterolemia will often die of MI before 20 years of age.
Understanding the role of the LDL receptors has led to the design of which family of drugs used to control cholesterol levels?
What is Cystic Fibrosis?
a disease caused by mutations in genes that encode for the chloride channel (receptor protein channels); causes viscous excretions in the lungs with extensive mucous plugging and dilation of tracheobronchial trees
What type of infection is commonly found in the lungs of someone who dies from Cystic Fibrosis complications?
Phenyketonuria, Galactosemia, and Lysosomal Storage Disease are three examples of diseases caused by mutations in ________.
What is Phenylketonuria?
an autosomal RECESSIVE disorder that causes a severe lack of phenylalanine hydroxylase and can lead to PKU or hyperphenylalaninemia
How common is Phenylketonuria?
1 in 10,000 Caucasian infants
True or False: Affected infants with phenylketonuria are normal at birth, but have impaired brain development due to decreased phenylalanine levels.
False: due to INCREASED phenylalanine (its not broken down)
How quickly does phenylketonuria cause mental retardation?
6 months of age
True or False: Restricting dietary sources of phenylalanine will prevent the development of mental retardation in those affected with phenylketonuria.
(early screening is mandatory in the US)
Lysosomal storage diseases commonly affect _____ and _____.
What accumulates in those children affected by lysosomal storage diseases?
accumulation of LARGE, insoluble molecules in macrophages (sphingolipids, mucopolysaccharides)
*this leads to hepatosplenomegaly
True or False: Lysosomal Storage diseases commonly involve the CNS.
Describe the pathogenesis of Lysosomal Storage Disease.
Normally, complex substrates are degraded by a series of lysosomal enzymes into soluble end products. If the enzymes are deficient or malfunctioning, catabolism is incomplete and the INSOLUBLE intermediates accumulate in the lysosome
What are three diseases that are associated with myelinated biproducts and sphingolipids?
Most mucopolysaccharide storage diseases (type of lysosomal storage disease) are autosomal _______.
(lack enzymes for degrading mucopolysaccharides)
Patients affected by mucopolysaccharide storage diseases will often have _________, ________, _________, and mental retardation.
coarse facial hair
clouding of the cornea
How many mucopolysaccharide storage disease variants are there?
MPS type I is called _______ Disease.
Hurler Disease (MPS 1) is caused by a deficiency of which enzyme?
If untreated, what is the life expectancy of Hurler Disease?
The cost of the Laronidase enzyme is more than $_________. What are other treatment options that could improve the outlook of the disease (not cure though)?
bone marrow transplant
MPS type II is called _______ Syndrome.
Hunter Syndrome is caused by a deficiency of which enzyme?
Hunter and Hurler are similar. Other than the enzyme deficit, how do they differ?
Hunter (type II)= no corneal clouding and milder clinical course than Hurler (type I)
What does it mean when a disorder is multifactorial (polygenic)?
two or more genes responsible, PLUS environmental influences
True or False: Many physiologic traits are multifactorial.
True, height, weight, blood pressure, and hair color
True or False: Many common diseases such as diabetes, hypertension, gout, schizophrenia, and bipolar disorder are purely genetically induced.
False, those listed disorders may all have polygenic influences from multiple genes and the environment
_______ is a composite of stained human chromosome strand pairs.
What is the normal chromosome count? Is it the same for males and females?
yes, it is the same. 23 pair total= 1 sex (either XX or XY) and 22 autosomal
How common are chromosomal abnormalities?
1 in 200 newborns
In as much as ____% of first trimester spontaneous abortions, the fetus has a chromosomal abnormality.
A normal chromosome count (2x23=46) is termed ______.
(Eu and Me...we have 23)
An increased chromosome count that is a multiple of the normal (3 x 23, or 4 x 23) is termed _______.
True or False: Polypoidy typically results in spontaneous abortion.
Any number of chromosmes that is not an exact multiple of the normal number is termed _______. Give an example.
*extra chomosome: trisomy = 2 x 23 +1 = 47
*absence of chromosome: monosomy = 2 x23 -1 = 45
Chromosome abnormalities can be of what two types?
What are structural abnormalities of chromosomes?
usually these result from chromosome breakage followed by loss or rearrangement of material
_______ is transfer of a part of one chromosome to another non-homologous chromosome
What is reciprocal translocation?
when fragments are exchanged between two chromosomes
What is chromosome inversion?
chromosome breaks in two points, then the released fragment is reunited after a complete turnaround
True or False: Trisomy 21 is a cytogenetic disorder involving autosomes.
What is the most common of chromosomal disorders?
Down's Syndrome (trisomy 21)
Down Syndrome is most closely related to what maternal characteristic?
45 years old = 1 in 25
Trisomy 21 results from ______ of chromosome 21 during formation of the ovum.
What are the physical/clincal traits that are associated with Down Syndrome?
flat facial profile
increased susceptibility to infection
increased risk of acute leukemia
True or False: Patients with Down Syndrome have increased susceptibility to severe periodontal disease in childhood.
Down Syndrome increases the risk for Leukemia by _____ to _____ times.
10 to 20 times
What are two cytogenetic disorders that involve sex chromosomes?
1. Klinefelter Syndrome
2. Turner Syndrome
How is the sex chromosome affected in Klinefelter?
two X chromosomes (at least) and one Y chromosome results in XXY genotype resulting in HYPOGONADISM
What are the physical characteristics that appear with Klinefelter Syndrome?
increased length of lower limbs
reduced body hair
hypogonadism (male sterility)
increased frequency of TUARODONTISM (large pulp chambers, be aware!)
Turner Syndrome results from _______.
partial or complete absence of one of the X chromosomes
True or False: Those patients with Turner Syndrome have a markedly tall stature.
False, markedly short
How many chromosomes will a patient of Klinefelter Syndrome have? Turner Syndrome?
Klinefelter: 47 chromosmes
Turner: 45 chromosomes
What are the physical characteristics associated with Turner Syndrome?
markedly short stature
webbing of the neck
low posterior hairline
congenital cardio malformations
primary amenorrhea and failure to develope secondary sex characteristics
Which cytogenic disorder of sex chromosomes will affect males? Which will affect females?
Turner: females (45, X)
Klinefelter: males (47, XXY)
What is FISH?
Fluorescence in Situ Hybridization
- uses fluorescent dye-labled probes that recognize sequences specific to chromosomal regions
What is comparative genomic hybridization?
uses different colored dyes attached to large segments of the test DNA and normal DNA, followed by hybridization. Relative amounts of each DNA sample are assessed on the color of the product and gene amplification or deletion can be identified in genetic diseases
What is a common method for molecular diagnosis of genetic disorders?
-amplification of DNA, then comparison of nucleotide order to normal DNA