4. Genetics Flashcards
Hcuc
Structural chromosomal abnormalities Plus examples
Results from chromosome breakage followed by loss or rearrangement of material
Can we both AutoSome or sex chromosomes
Translocation
Isochromosomes
deletion
inversion
ring chromosome
Translocation plus example
Chronic myelogenous leukemia t(9:22)
Burkitt lymphoma t(8:14)
robertsonian translocation
May results Down’s syndrome t(14:21)
deletion
Cri du chat syndrome(del 5p or 5p-)
13q 14 (Retinoblastoma)
11p 13 (WAGR complex [Wilms tumor, Aniridia, Genitourinary anomalies, and mental Retardation] ) .
22q11.2 Deletion Syndrome(DiGeorge syndrome and velocardiofacial syndrome
isochromosome translocation
Turner’s Syndrome (isochromosome of the
long arm of the X chromosome).
ring and inversion
not severe
Cri du chat
Congenital deletion on short arm of chromosome 5 (46,XX or XY, 5p−).
symptoms
microcephaly, moderate to severe intellectual disability, high-pitched crying/meowing, epicanthal folds, cardiac abnormalities (VSD).
Numerical Chromosomal Abnormalities
Is caused by a loss or a gain of chromosomes, resulting in a karyotype known as aneuploidy.
Instead of the normal diploid number of chromosomes, the karyotype may be hyperdiploid (2n+1, 2n+2, etc.) or hypodiploid (2n-1, 2n-2, etc.)
numbers
monosomy (2n-1)
trisomy (2n+1)
nullisomy (2n-2) if same chromosome
double monosomy (2n-1-1) if d/t chromosomes
tetrasomy (2n+2)
double trisomy (2n+1+1)
causes of aneuploidy
non disjunction
anaphase lag
mosaisicm
Trisomy 21 (Down’s Syndrome)
Pathogenesis
95% of maternal origin often in older women
96% nondisjunction and
4% Robertsonian translocation (e.g., 22 or 14)
symptoms of down syndrome
Diseases that seen with high frequency in down syndrome
hematologic-
Neurological
abnormal transient myelopoieis (transient leukemia) < 3 months
acute leukemia types
ALL-acute lymphoblastic leukemia > 5 years
AML-acute myeloid < 5 years
alzheimers because b amyloid precursor gene is from chromosome 21 so early alzheimers
trisomy 18 symptoms
trisomy 13 symptoms
numerical abnormality in sex chromosome
turnner and kleinflider
turner syndrome
1 X chromosome 45 chrom
A common cause of female hypogonadism
These women never experience puberty and do not develop secondary sex characteristics
Infertility is the norm( the second X chromosome is necessary for oogenesis and normal development of the ovary)
Isochromosome of the X chromosome 15%
turner syndromes list
Klinefelter’s Syndrome
A common cause of male hypogonadism
80% are 47,XXY
20% 48,XXXY, 49,XXXXY, or mosaic 47,XXY/46, XY
Caused by meiotic nondisjunction
single gene mutation part
tree pic
difference between autosomal dominant and recessive
tree
Reduced penetrance refers to
Reduced penetrance refers to the situation where an individual inherits a genetic mutation that causes an autosomal dominant disorder, but does not show any symptoms or signs of the disease.
examples of autosomal dominant
marfan syndrome general
Mutation of FBN1 gene (ch15) results in defective fibrillin, a glycoprotein that forms a sheath around elastin. This protein acts like a glue in connective tissues.
fibrillin also reduces TGF-B (Tissue growth factor) so no fibrillin means over production of tissue
marfan syndrome symptoms
MARFANS
mitral valve prolapse
aortic aneurysm
retinal detachment
FBR1 mutation
Arachinodactyl
n
subluxated lens upward and outward plus scoliosis
familial hypercholestolemia general
Mutation in the low density lipoprotein (LDL) receptor gene on chromosome 19
The cholesterol levels in the blood remain high, even though the HMG-CoA reductase enzyme is inhibited by the cholesterol. This leads to a loss of feedback inhibition of HMG-CoA reductase and an increased synthesis of cholesterol.
and increased phagocytosis of LDL by macrophages.
FHC symptoms
tendon xanthoma
xanthelasma
cornial arcus
atheroscelerosis
autosomal recessive disorders example
Cystic fibrosis
storage diseases- alkaptonuiria
- homocysteinuria
- glycogen storage disease
- lipid storage disease - tay sachs disease
-
cystic fibrosis general
Mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene
The functions of CFTR are tissue-specific means …?
CFTR codes for chloride and na channels so no CFTR gene means no channels
in sweat glands no re absorption of na and cl to the lumen so sweat is salty
in git and respa no Na and Cl secretion to the lumen so GI stuff very viscous and mucuous very viscous
CF symptoms
respa
recurrent pnemonia (pseudomonas aergunosa)
chronic bronchitis
lung abscess
blocked airway thick mucus
GI
meconeum ileus in infants
malabsorption
pancreatitis
liver dieases secondary to bilary duct obstruction
others
salty sweat
obstruction of vas deferens
storage disease example
alkaptonuria
homocysteinuria
alkaptoneuria (ochronosis)
Deficiency of homogentisic acid oxidase (Ch 3q21-q23) results in the accumulation of homogentisic acid
HA + oxygen ~ black
One of the most distinctive features of alkaptonuria is darkening of the urine, which occurs due to the presence of HGA. Over time, HGA can also accumulate in the body’s connective tissues, such as cartilage and tendons, leading to a condition called ochronosis. Ochronosis can cause joint pain and stiffness, as well as skin discoloration.
alkaptonuria symptoms
ochronosis of sclera , ear
brown to black urine
arthritis
homocysteinuria general plus symptoms
Due to deficiency of cystathionine synthetase (Ch 21q22)
marfan syndrome symptoms plus
mental retardation and lens downward and inward
homocystein accumulate leading to
atheroscelerosis
glycogen storage disease
15 types
but type 1 2 3 5 are autosomal recessive
PAS stain
lipid storage disease
Disorders of lipid metabolism are due to a missing lysosomal enzyme.
They are a component of lysosomal storage diseases.
Lipid can be stained by oil red O or Sudan Black B.
examples of lipid storage diseases
tay sachs disease
neimann pick disease
gaucher disease
Tay sachs disease general
lipid storage disease
mutation in chromosome 15 which codes for hex A enzyme which degrades GM2 gangliosides
defect in the enzyme results in the accumulation in nerve and cns
tay sachs disease symptoms
low muscle tone
seizures
progressive neurodegeneration
motor mental viusal deterioration
cherry red spot in macula densa
neimann pick disease general plus symptoms
type a and b
deficiency in sphingomylinase
sphingomylin accumulate in macropages and form foam cells
Like Tay-Sachs disease involves the retina (cherry red spot) and central nervous system.
Un like Tay-Sachs involve reticuloendothelial system (hepatosplenomegaly, lymphadenopathy, and bone marrow involvement)
type c
ataxia, dysarthria and psychomotor regression and increases the risk for Alzheimer disease
gaucher disease general
Deficiency of Glucocerebrosidase or glucosylceramidase -Ch1
glucocerebrosidase degrades glucocerebroside
so deficiency causes accumulation in macrophages
‘Gaucher cells’
macrophages has a characteristic fibrillary or wrinkled tissue paper appearance
in neimann pick faom cells with vacoules
gaucher disease symptoms
mainly REC so
hepatosplenomegaly
pancytopenia
bone erosions and fractures (like femoral neck fracture)
lymphadenopathy
summary of lysosomal storage disease
pivtutre slide 34
sex linked disorders charachteristics
All sex-linked disorders are X-linked and almost all are recessive
No Y-linked diseases are known (males with mutations affecting the Y-linked genes are usually infertile)
In males many recessive genes of the X chromosome will be expressed as if they were dominant
Heterozygous females rarely express the complete phenotype (normal allele inactivation) of the disease as they have the paired normal allele
An affected male does not transmit the disease to his sons, but all his daughters are carriers
x linked dominant and x linked recessive difference
pic
x linked reccesive disorders example
Single Gene Disorders With Nonclassic Inheritance
some single gene disorders do not follow these classic patterns of inheritance and are classified as having nonclassic inheritance.
examples of single gene non classic inheritance
Codominant disorders
Diseases Caused by Trinucleotide-Repeat Mutations
mitochondrial DNA disorders
Disorder of imprinting
gonadal mosaisicm
why is alpha 1 antitrypsin deficiency called codominant
both gene from parents should be mutated
if both genes normal 100% effective anti trypsin (pM)
if 1 gene deffective onely 50%+10% effective which is enough to lead normal life (pS)
if both genes are mutated only 20% effective so leads to deficiency (pZ)
alpha 1 anti trypsin general
anti trypsin is an enzyme which reduces the activity of proteases
neutrophils produce proteases to degrade infection but also in lungs they eat the elastase whic leads to panacinar emphesema
anti trypsin avoids this
also defected AAT builds up in liver because its produced there so causes cirrohsis
chromosome 14
genetic anticipation
Genetic anticipation is a phenomenon in which the severity and/or age of onset of a genetic disorder tends to worsen or occur at an earlier age in subsequent generations within a family.
Diseases Caused by Trinucleotide-Repeat Mutations
Particularly cause neurodegenerative disorders
Trinucleotides usually share the nucleotides G and C
May show genetic anticipation
examples of diseases caused by trinucleotide repeat mutations
fragile X syndrome
fragile x syndrome general
mutation in FMR1 gene (fragile mental retardation gene)
in that gene CGG repeats which leads to its methylation so inactivation so condensation
X chromosome looks fragile in karyotype
affects male mostly
iq 20-60
fragile x chromosome symptoms
Post pubertal macroorchidism
long face with a large jaw
large everted ear
autism
mitral valve prolapse
hypermobile joints (become more obvious with age)
“Big testes, big face, big ears, autism, prolapsed valve, and joints that are hypermobile.”
mitochondrial DNA disorders
Principally affect tissues with high energy requirements (e.g., the central nervous system, heart, and skeletal muscle)
Transmitted only through the mother. All offspring of affected females may show signs of disease. Variable expression in a population or even within a family due to heteroplasmy
heterosplasmy
Heteroplasmy refers to the presence of two or more different types of mitochondrial DNA (mtDNA) within a single cell or individual. This can occur due to mutations in mtDNA that are present in some, but not all, mitochondria within a cell or tissue.
Leber hereditary optic neuropathy (LHON)
It is caused by mutations in mitochondrial DNA (mtDNA) that lead to a loss of function in the mitochondria within cells in the optic nerve, which can lead to optic nerve atrophy and vision loss.
first noted between ages 15 and 35
also cardiac problems seen
Imprinting plus how
Imprinting is epigenetic process selectively inactivates either the maternal or the paternal allele of some genes.
by
methylation at CG nucleotide
histone deacetylation
methylation
imprinting disorder example
prader willi syndrome and angelman syndrome
prader willi syndrome and angelman syndrome
pic
gonadal mosaisicsm general
