Lecture 1- Genetic Diseases Flashcards
there are … protein-encoding genes in the human genome
19,000
… refers to a permanent change in DNA
mutations
Mutations affecting germ cells can be..
inherited
Mutations affecting somatic cells may result in … or … abnormality
tumor
developmental
3 types of mutations
point
frameshift
trinucleotide repeat
A … mutation is when a single base is substituted
point
A … mutation is when there is an insertion/deletion of 1-2 base pairs
frameshift
A …. mutation is when there is amplification of a 3-nucleotide sequence
trinucleotide repeat (fragile X syndrome)
3 other types of alterations other than mutations
polymorphisms
epigenetic changes
alterations in non-coding RNAs
… disorders are diseases caused by single gene defects and they can be 3 different types:
mendelian
autosomal dominant
autosomal recessive
sex-linked (X -linked)
do autosomal dominant disorders usually have outward physical changes?
yes but may be delayed onset
In autosomal dominant disorders, …. is when a person has a mutant gene, but doesn’t or only partially expresses it phenotypically
reduced or incomplete penetrance
In autosomal dominant disorders, … is when expression can be identified in all affected persons but to differing extents
variable expressivity
In autosomal dominant disorders, … is when neither parent is affected of theres no family history
new or “de novo” mutation
…. is an autosomal dominant disease with nearly 100% penetrance– and its relatively common (1/… live births) condition
Neurofibromatosis
3000
T/F: Neurofibromatosis has highly variable expressivity
true
… … disorders is the largest group of mendelian disorders
autosomal recessive
affected patients of autosomal recessive disorders are…
homozygous
In autosomal recessive disorders, …% of offspring are affected and …% of offsrping are carriers
25%
50%
Many AR conditions are enzyme defects, leading to ….
metabolic dysfxn
Age of onset for AR is usually… and … penetrance is common
early
complete
Sex linked disorders are all on the … chromosome
Y chromosome only has 1 significant gene –
X
SRY sex determining region
Most X linked disorders are …
recessive
… is the process in which 16 days post conception, most (>75%) of one X chromosome is randomly inactivated (resulting in formation of a Barr body) in all of the cells within the zygote
Lyonization
…. is when there is a random inactivation of an abnormally high number of normal X chromosomes resulting in X-linked disease expression in a heterozygous female
unfavorable lyonization
… is an autosomal dominant disorder of connective tissue due to mutation of the FBN1 gene, resulting in abnormal fibrillin, a glycoprotein necessary for normal elastic fiber production
Marfan syndrome
Someone who has the following traits have what disorder?
tall, thin abnormally long legs arachnodactly dislocation of eye lens aortic aneurym/dissec.
marfan syndrome
At least 6 different types of …. syndrome may exist, probably because this is a problem of collagen synthesis, and there are about 30 different types of collagen
Ehlers-Danlos
2 syndromes caused by mutations in structural proteins
marfan
ehlers-danlos
Frequency of familial hypercholesterolemia is 1 in
500
… is an autosomal dominant disorder that is a mutation of the gene that encodes the LDL receptor
familial hypercholesterolemia
Patients with familial hypercholesterolemia have multiple… of the skin and premature …
xanthomas
atherosclerosis
Heterozygotes of FH have a …. increased amount of …
2-3x
LDL
Homozygotes of FH have over … normal levels of LDL and often die of MI by 20
recent approval of …. to treat homozygous form
5x
lomitapide
3 diseases caused by mutations in enzyme proteins
phenylketonuria
galactosemia
lysosomal storage diseases
Phenylketonuria is an autosomal …. disorder that affects 1 in …. caucasian infants
recessive
10,000
Phenylketonuria is a lack of …. that leads to … and …
phenylalanine hydroxylase
hyperphenylalanemia
PKA
Affected infants of Phenylketonuria are normal at birth but elevated levels of phenylalanine impair… and … is evident at 6mo. Screening in the US is mandatory
brain development
mental retardation
treatment of phenylketonuria
restricting dietary sources of phenylalanine intake will prevent mental retardation
lysosomal storage diseases are by autosomal …. transmission
recessive
mucopolysaccharide is a …. disease
lysosomal storage
Mucopolysaccharide storage disease is due to lack of one of the several enzymes necessary to degrade
mucopolysaccharides
affected patients of mucopolysaccharide of ten have…
coarse facial features
cornea clouding
joint stiffness
mental retardation
MPS type I disease is called…. and it is caused by a deficiency of …
Hurler disease
alpha-L-iduronidase (laronidase)
The life expectency of Hurler disease is … if left untreated
6-10 years
…. or …. may improve outlook of Hurler disease but not all aspects of disease are corrected
bone marrow transplant
enzyme replacement
Cost of enzyme to trreat hurler disease can be about …. annually
300K
… is MSP type II and is X-linked and is a deficiency of L-iduronate sulfatase. It is similar to Hurler as far as symptoms go except there is no cornea clouding and is milder overall
Hunter disease
It’s estimated that 1 in … newborns have a chromosomal abnormality
200
In as many as … % of 1st trimester spontaneous abortions, the fetus has a chromosomal abnormality
50%
The term … means a normal chromosome count (2x23=46)
euploid
The term…. is an increased chromosome count that is a multiple of that normally seen (3x23 or 4x23) and generally results in spontaneous abortion
polyploidy
Any number that is not an exact multiple of the normal chromosome count is termed …
examples include an extra chromosome (trisomy, 2x23 +1= 47) and absence of a chromosome (monosomy 2x23-1=45)
aneuploidy
… is transfer of a part of one chromosome to another nonhomologous chromosome (can be reciprocal)
translocation
… is loss of a portion of a chromosome
deletion
… is when a chromosome breaks in two points then the released fragment is reunited after a complete turnaround
inversion
…. is most common of the chromosomal disorders and is associated with advanced maternal age
trisomy 21 (downs)
If mother is younger than 20 then there is a 1 in … chance of downs
1550
If mother is older than 45 then there is a 1 in… chance of downs
25
downs syndrome is due to meiotic non-disjunction of …. during ovum formation
chromosome 21
Clinical manifestations of downs
mental retardation
epicanthic folds (eyes slant down)
flat facial profile
cardiac malformations
increased susceptibility to infection (early perio disease)
large tongue
increased rick (10-20x) of acute leukemia
2 cytogenetic disorders involving sex chromosomes
Klinefelter syndrome
Turner syndrome
… is defined as male hypogonadism that develops when there are at least 2 X chromosomes and one or more Y chromosomes (most are 47 XXY)
Klinefelter syndrome
The clinical manifestations of Klinefelter syndrome are…
increased length of lower limbs
reduced body hair
gynecomastia
taurodontism
… is due to partial or complete absence of one of the X chromosomes
Turner syndrome
Clinical manifestations of turner syndrome
Short
Webbing of neck/low posterior hairline
Shield-like chest (broad)
high arched palate
congenital CV malformations
failure to develop secondary sex charac.; primary amenorrhea
Indications for prenatal genetic analysis
mother older than 34
parent is carrier of a chromosomal translocation or Xlinked disorder
hx of previous child with chromosomal abnormality
Indications for genetic analysis postnatally
multiple congenital anomalies
unexpl. mental retard, or develop. delay
suspected aneuploidy
suspected sex chrom. abnormality
infertility
multiple spontaneous abortions
