Exam 1: Ch 6 Flashcards
__ pairs of autosomes
22
__ pairs of sex chromosomes
1 pair
genetic diseases are caused by…
mutations in DNA sequence
chromosome-level abnormalities
gene
DNA that codes for a protein
locus
gene location on a chromosome
allele
alternate version of a gene
homozygoes
2 identical alleles for a gene
heterozygous
2 different alleles for a gene
genotype
genetic composition
dictates phenotype
phenotype
observable trait/characteristic
dominant traits
traits that are expressed in heterozygous
only need one dominant allele to be expressed
recessive traits
traits expressed only in the homozygote with 2 recessive alleles
co-dominant
both alleles are expressed in the heterozygote
ex. blood type… A,B are codominant
how many alleles for blood type?
3
A, B, O
blood type genotypes and phenotypes
AA, AO = type A
BB, BO = type B
OO = type O
AB = type AB
single gene disorder
mutation in 1 gene
autosomal or sex-linked
sex-linked disorder
almost always on X chromosome and generally recessive
Punnett square mom/dad
mom’s alleles are horizontal
dad’s alleles are vertical
can you use the term carrier to describe dominant traits?
no, b/c 1 dominant allele gives you the trait
examples of autosomal dom. disorders
achondroplasia
adult polycystic kidney disease
huntington chorea
familial hypercholesterolemia
marfan syndrome
neurofibromatosis (NF)
examples of autosomal recessive disorders
cystic fibrosis
oculocutaneous albanism
phenylketonuria (PKU)
sickle cell disease
tay sachs disease
examples of x-linked recessive disorders
hemophilia A
R/G colorblindness
Fragile X
Bruton type hypogammaglobulinemia
Duchenne dystrophy
autosomal dominant disorders
single mutant allele inherited from either parent –> disease
commonly involve abnormal structural or developmental proteins
transmission equally likely to male/female children
variable penetrance
not everyone who gets the gene expresses it
variable expressivity
variation in how severely a trait is expressed
new mutations can arise…
affected person does not have an affected parent
Marfan’s syndome
autosomal dom. connective tissue disorder (defect in structural protein)
mutation of FBNI gene that codes for fibrillin I, a component of elastin fibers
many different mutations possible… no genetic diagnosis
symptoms of Marfan’s syndrome
long thin fingers (arachnodactyly)
spinal deformities (kyphoscoliosis)
lens dislocation from weakness is suspensory ligaments
pectus excavatum
dilation and aneurysm of the aorta (life threatening)
neurofibromatosis
autosomal dom. mutation of gene that regulates cell growth
can also appear as a new mutation
neurogenic tumors from Schwann cells and elsewhere in PNS
NF-1 or NF-2
NF-1
chromosome 17, more common
cutaneous and subQ neurofibromas on trunk and elsewhere
skeletal lesions (scoliosis)
neuro-endocrine tumors (polychromocytoma)
NF-2
chromosome 22
tumors of acoustic nerve (vestibulocochlear) VIII
headache, hearing loss, tinnitus
do autosomal dom. or rec. skip generations?
recessive
homozygous recessive disorders
often involve enzyme deficiencies
if both parents are carriers, 1/4 kids have disease, 1/2 are carriers
incest increases risk
heterozygotes may or may not be abnormal but will not have the disease
phenylketonuria (PKU)
autosomal recessive deficiency is hepatic enzyme phenylalanine hydroxylase (phenylalanine to tyrosine)
phenylalanine builds up in the blood
multiple defects possible, some only cause mild disease
diagnosis, symptoms, and treatment of PKU
measure serum phenylalanine
mental retardation if untreated
restrict phenylalanine in infants/pregnant women
Tay-Sachs disease
autosomal recessive lysosomal storage disease
caused by absense of enzyme that metabolizes gangliosides in cell membrane
lipids (gangliosides) accumulate in cells of the brain
causes deterioration in mental function and death by 4 years of age
X-linked traits
on x chromosome and often recessive
if recessive more common in males than females
males transmit gene only to daughters
females transmit gene equally to sons and daughters
hemizygous
males, x-linked trait term
p arm is long or short?
short
q arm is long or short?
long
genomic imprinting
some genes inherited from both parents but only the allele from 1 parent is expressed
non-expressed alleles can be passed on and expressed in later generations
DNA is modified by methylation –> causes gene to not be expressed
paternal imprinting
allele from father is not expressed due to methylation
maternal imprinting
allele from mother is not expressed due to methylation
Angelman syndrome
paternal imprinting
Del 15q12 –> loss of ubiquitin path gene
hyperactivity, autism, seizures
Prader-Willi
maternal imprinting
triplet repeat mutation example
fragile X syndrome (also Huntington)
mental retardation and distinct facial features (prominant jaws, large ears)
mutation of RNA binding protein found on X chromosome
expansion of CGG repeats
more common and severe in males
triplet repeat explanation
DNA has areas of repeat sequence
chromosomes don’t line up correctly
if you get too many repeats, you get the disease
mitochondrial gene disorders
mitochondria contain genes for oxidative phosphorylation
inherited from mother (most mitochondria in egg, not sperm) only to 100% of offspring
mostly impacts tissues with high metabolic rate
multifactorial genetic disorders
caused by more than 1 gene and environmental factors
inheritance patterns are less clear cut, and it’s hard to predict phenotypes
risk greater if a close relative has the disorder
the closer the relative the greater the risk
cleft lip/palate
multifactorial genetic disorder
varies greatly in severity of expression – could have just lip or palate
commonly produces speech and feeding problems
during meiosis, diploid chromosome number is reduced to _____
haploid
fertilization reestablishes the diploid genome
mosaic
errors early in mitotic development
some daughter cells are normal and some are not
how harmful depends on the activity of the cell (less than 5% is not bad, 75% could be bad)
aneuploidy
abnormal chromosome number
gametes may lack a chromosome or have 2 copies
caused by nondisjunction (chromatids do not separate in meiosis II)
monosomy
1 copy of a chromosome post-fertilization
triosmy
3 copies of a chromosome post-fertilization
breaks in chromosomes can produce
structural abnormalities
parts either deleted or rearranged
causes are x-rays, chemicals, viruses
deletion
part of a chromosome is lost
translocation
material moves from 1 chromosome to another
balanced: no material lost
Robertsonian: short arms lost… 14 & 21 can –> DownS 5%
isochromosomal translocation
during meiosis 1, two chromatids connect
short and long arms fuse
2 chromatids separate in meiosis 2
inversion
part of chromosome inverted
ring formation
single chromatid’s ends unite to form a ring
consequences of chromosomal abnormalities
depends on how much genetic material is affected
cells may undergo apoptosis
can contribute to cancer
in gametes can produce congenital defects
down syndrome causes & risk factors
trisomy 21 (95%)
robertsonian translocation of 14 & 21 (5%)
older maternal age (oogenesis arrest in diplotene phase)
down syndrome symptoms
variable level of MR
characteristic facial features, poor growth, protruding tongue, hypotonia
heart & GI defects
80% of dementia in aduthood
down syndrome screening and definitive test
screening: low alpha-fetoprotein, high HCG, low unconjugated estriol
tests: aminocentesis, chorionic villus sampling, umbilical cord blood sampling
what causes dementia in down syndrome
beta-amyloid plaques – breakdown of APP on chromo 21
3 copies so can’t make more APP + more broken down
turner syndrome
x-chromosome monosomy 45, X most common
mosaicism also possible (45, X or 46, XX)
short stature female without secondary sex characteristics or menstruation
congenital cardiac and renal abnormalities
turner syndrome treatment
growth hormone and estrogen therapy in early childhood
Klinefelter’s syndrome
47, XXY or 48, XXXY
male phenotype with deficient secondary sexual development and infertility
tall
androgen therapy
each ____ _____ is vulnerable at different times during development
organ system
teratogenic agents
environmental agents that cause abnormal embryonic development
radiation: skeletal/neruo abnormalities
chemicals: Hg, ETON, cocaine, anti-cancer meds, thalidomide
folic acid deficiency –> neural tube defect
infectious agents: toxoplasmosis (protozoa in cat litter), rubella, other viruses
fetal alcohol syndrome
drug induced developmental abnormality caused by EtOH consumption during pregnancy
physical, cognitive, and behavioral abnormalities
growth retardation, developmental delay, characteristic facial features
severity determined by amount of EtOH consumed, and at what time during pregnancy
goals of prenatal screening
detect fetal abnormalities
provide pt info needed to make informed decisions
provide reassurance to members of high-risk groups
methods of prenatal screening
ultrasound
maternal blood screen
aminocentesis
chorionic villus sample
fetal blood sample
it is now possible to detect ____ ____ or ___ ___ in maternal circulation
fetal cells or nucleic acids
noninvasive of fetus, early application, paternal DNA easiest to assay
ultrasound
finds NTD, spina bifida, hydrocephalus, heart defects
maternal blood screen
AFP (fetal protein) increase in maternal blood in NTD, also HCG for Downs
aminocentesis
amniotic fluid contains fetal cells
finds chromosomal abnormalities (Downs)
chorionic villus sampling
fetal tissue for chromosomal and genetic analysis
fetal blood sample
finds fetal blood abnormalities and infections
think mitochondrial disease when ___+ organ systems are involved
3+
myoclonic epilepsy with RRFs
SRY gene on Y chromosome
if nonfunctioning, can be XY and female phenotypically
Periods of vulnerability
CNS 2-5 wks
Heart 3-6 wks
Extremities/eyes 4-7 wks
External genitalia 6-10 wks
Periods of vulnerability
CNS 2-5 wks
Heart 3-6 wks
Extremities/eyes 4-7 wks
External genitalia 6-10 wks
