genetics Flashcards
types of prenatal genetic analysis
Karyotype, FISH, microarray, genome sequencing
how many generations should be tested in the genetic work-up?
2-3 generations
what should be used in the standard pedigree info?
initials/names of family ages or DOB ages and cause of death details of a disorder min of 2-5 generations ethnic background including religious group
who are at-risk family members?
consanguinity ashkenazi jews african, mediterranean BRCA caucasians
what is termed as the physical location of a gene?
locus
what is the version of a gene? letter used to represent a gene
allele
what is considered a “normal” allele?
wild-type
what is considered an abnormal version of the gene associated with a trait/disorder?
mutant
structures which house the gene
chromosome
how many chromosomes do we have?
46 (23 pairs)
what is the “central dogma”
process of replication, transcription and translation
what is the message(nucleotides) encoded in RNA called? 3 letter words
codon
what are the first 22 pairs of chromosomes called?
autosomes
What are a combination of alleles at adjacent locations on a chromosome that are inherited together. Or a set of single-nucleotide polymorphisms
haplotype
Production of RNA using DNA code as template
transcription
Production of a protein using RNA code as template
Translation
Actively forming the string of proteins in to a 3D form that can be used by the body
folding
sites at which a single letter in the DNA code has been swapped for a single alternate letter
single nucleotide polymorphisms (SNPs)
Produces a new cell with the same number of chromosomes as the original
mitosis
Occurs in Germ cells, Two phases
meiosis
Occurs with autosomes (somatic)
mitosis
most compact phase of mitosis?
metaphase
two nuclear membranes form in which stage of mitosis?
telophase
The centromere splits, start to draw to opposite ends during which stage of mitosis?
anaphase
This is when different mutations occur on the same gene
allelic heterogeneity
This occurs when different genes cause the same disease (e.g. hearing loss)
Locus/non-allelic heterogeneity
This occurs when different phenotypes occur with mutations on the same gene (e.g. RET gene lic heterogeneity associated with Hirschprungs and Multiple Endocrine Neoplasia)
Phenotypic heterogenity
what is penetrance?
when you inherit the gene, but are “normal” - incomplete penetrance (Ex BRCA)
what is expressivity?
seen in all that have the gene, but expressed differently (variable expressivity, such as Marfan’s)
Increased severity in subsequent generations
CNS disorders
Trinucleotide repeat expansion
HD, Myotonic dystrophy
anticipation
what is x-linked?
no male to male, all daughters of males are carriers
what is co-dominance?
both alleles of the gene pair contribute to the phenotype (blood groups)
what are examples of non-mendelian inheritance?
genomic imprinting
mosaicism
mitochondrial DNA mutations
autosomal dominant disorders
huntington disease myotonic dystrophy Neurofibromatosis,Tuberous Sclerosis Urinary Polycystic Kidney Disease, Familial Adenomatous Polyposis, Marfan’s syndrome Ehlers-Danlos syndrome
Autosomal Recessive Disorders
Cystic Fibrosis Sickle Cell Anemia Tay-Sachs Disease Phenylketonuria (PKU) Galactosemia Homocystinuria Lysosomal storage disease Fredereich ataxia Spinal muscular atrophy
X-Linked Disorders
Male-hemizygous (Y not homologous to X)
Heterozygous female can manifest some symptoms (less than male)
Example: G6PD deficiency
example of y-linked disorder
sertoli-only cell syndrome (complete absence of germ cells in testis)
what are mitochondrial disorders?
maternal inheritance, leber hereditary optic neuropathy
what is mosaicism?
Mitotic errors develop early and result in two or more populations of cells with different chromosomal information in the same person.
Common in X, Y
Occurs post-zygotically
This chromosome occurs when two broken ends of the same chromosome fuse
ring
This is when a chromosome breaks and the fragment re-attaches to the original chromosome in a reverse orientation
inversion
This is when a chromosome lacks certain genes or there is an absence of a segment of DNA.
deletion
I am a point mutation that exhanges a nucelotide for another one= changes in amino acids. may affect protein function
missence
sickle cell disease is an example of what type of mutation?
missence
I am a point mutation changing a codon for an amino acid into a STOP codon.Usually non-functional
nonsense
autosomal dominant disorder characterized by the development of bilateral vestibular schwannomas. average age of onset is 18-24 years
NF2 (bilateral acoustic neurofibromatosis, or central NF)
autosomal dominant disorder which manifests in the 3rd or 4th decade and leads to complaints of muscle stiffness and is evidenced by the marked delay that occurs before affected muscles can relax after a contraction
myotonic dystrophy
what is the most life threatening inherited disease worldwide? characterized by numerous fluid-filled cysts that result in massive enlargement of the kidneys
polycystic kidney disease
difference between Autosomal Recessive Polycystic Kidney disease and autosomal dominant
autosomal recessive is a disease of childhood and linked to hetogenous mutations in a single gene.
autosomal dominant mostly seen in adults which leads to uncontrolled/regulated cell growth
Gene that provides instructions for making a protein called fibrocystin (sometimes known as polyductin) which is present in adult and fetal kidney cells.
PKHD I
what is the function of PKHD I that we are concerned with in PKD?
cell proliferation
autosomal dominant disorder where the person will have hundreds to thousands of adenomatous polyps in the colon and has a nearly 100% risk of developing CA by middle age if colon is not surgically removed
Familiar Adenomatous polyposis (FAP)
what do FAP patients present with?
numerous colorectal ademonas by the second or third decade of life
autosomal dominant disorder which causes defects in in collagen and other proteins of various tissues. patients will have skin elasticity, joint hypermobility, tissue fragility, multiple ecchymoses, and subcutaneous pseudotumors
Ehlers-Danlos Syndrome
autosomal dominant connective-tissue disorder. cardinal features: tall stature, ectopia lentis, mitral valve prolapse, aortic root dilation, and aortic dissection
marfan syndrome
what percentage of marfan’s patients have an affected parent?
3/4
is marfan syndrome fully penetrant?
yes
marfan syndrome results from mutations in which gene?
fibrillin I gene which encodes for the glycoprotein fibrillin - a major building block of microfibrils, which constitute the structural components of the suspensory ligament of the lens
abnormalities involving microfibrils in marfan’s weaken what?
the aortic wall, which leads to progressive aortic dilation and eventual aortic dissection
4 major diagnostic findings for marfan syndrome
dilation or dissection of the aorta@ level of the sinuses of valsalva
ectopia lentis
dural ectasia
4 or 8 specific skeletal features
autosomal dominant. this is the “receptor disease” caused by a mutation of the gene encoding the receptor fo rLDL, which is involved in the transport and metabolism of cholesterol
familial hypercholesterolemia - as a consequence of the receptor abnormalities there is a loss of feedback control and the patient will develop elevated cholesterol levels. 1 in 500 individuals
- heterozygotes with one mutant gene: 2-3 fold elevation in plasma cholesterol
- Homozygotes: most severely affected, 5-6 fold increase in plasma cholesterol levels
co-dominant disorder where there is a deficiency of the protease inhibitor alpha I-antitypsin which results in a predisposition to pulmonary emphysema and hepatic cirrhosis. accounts for approximately 2% of COPD cases in america
alpha I antitrypsin Deficiency
autosomal recessive disorder caused by a defect in the PAH gene which codes for pheylalanine hydroxylase, an enzyme that converts phenylalanine to tyrosine in the liver. part of newborn screen, with strict adherence to diet can avoid most of the symptoms.
PKU
clinical signs/symptoms of PKU
fair skin, blonde hair, blue eyes.
mental retardation, hyperactivity, seizures and eczema characterize untreated patients. hallmark sign “mousy” odor of hair, skin and specifically urine
treatment of PKU
restrict dietary pheylalanine and supplement tyrosine
autosomal recessive disorder caused by almost total I-phosphate uridyl transferase deficiency. accumulation of galactose I-phosphate which results in injury to parenchymal cells of the kidney, liver and brain
galactosemia
Tx is a galactose free diet
autosomal recessive disorder involving a gene that is involved in copper transport. leads to increased copper storage and ultimately liver disease
wilson’s disease
when does wilson’s disease first appear?what is the initial feature?
between ages of 6 and 40. liver disease (jaundice, fatigue, loss of appetite and abdominal swelling)
autosomal recessive disease causing hexosaminidase A deficiency. Ashkenazi jews. relentless deterioration of mental and physical abilities which commences at six months of age and usually results in death by the age of four
Tay Sachs
*no treatment for these patients
most common cause of inherited MR
fragile X syndrome
clinical features of fragile X
large protruding ears large testes elongated face stereotypic movements (hand flapping) CGG trinucleotide repeated
chromosomal abnormality involing absence of all or part of one X chromosome (X monosomy). most common sex chromosome abnormality of human females. (45, XO karyotype)
turner syndrome
keys to diagnosis of turner syndrome
short stature with normal GH levels
hypogonadism
primary amenorrhea or early ovarian failure
epicanthal folds, webbed neck, short fourth metacarpals
renal and cardiovascular anomalies
syndrome characterized by severe hypotonia and feeding difficulties in early infancy followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity
prader willi syndrome
down’s syndrome, major cause of mental retardation. chromosome count is 47
trisomy 21
characteristics of trisomy 21
Flat facial profile
Oblique palpebral fissures
Epicanthic folds
Predisposed to Leukemia, Congenital Heart disease and early Alzhiemers
edwards syndrome, associated with severe intellectual disability, many infants die within their first month
Low birth weight Small, abnormally shaped head small jaw and mouth Clenched fists with overlapping fingers; heart defects Abnormalities of other organs.
trisomy 18
patau syndrome. nearly 50% die within the first month, relatively few survive past 3 years of age
Holoprosencephaly
Eye anomalies (microphthalmia, anophthalmia, or coloboma)
Cleft lip and palate
Polydactyly
Cardiac defects
Low birth weight
trisomy 13
characterized by an extra copy of the Y chromosome in each of a man’s cells. may be taller than average
XYY - most males with this have normal sexual development and are able to father children
Associated with an increased risk of learning disabilities and delayed development of speech and language skills.
Delayed development of motor skills (such as sitting and walking), hypotonia, motor tics, and behavioral and emotional difficulties are also possible.
These characteristics vary widely among affected boys and men
trisomy X, characterized by the presence of an additional X chromosome in each of a female’s cells. may be taller than average
XXX
one of the most frequent forms of genetic disease involving the sex chromosomes as well as one of the most common causes of hypogonadism in males.
Klinefelter syndrome - rarely diagnosed before puberty
this is a component of the 22QII deletion syndrome
DiGeorge syndrome - fairly common (1 in 4,000), often missed because of variable clinical features
clinical features of DiGeorge Syndrome
congenital heart defects abnormalities of the palate facial dysmorphism developmental delay Variable degrees of T-cell immunodeficiency Hypocalcemia
