Locus
the specific location of a gene on a chromosome
Alleles
different versions of a gene, humans have 2 alleles for each autosomal gene
What is a gene?
hereditary units of DNA transmitted from one generation to another, code for proteins
What are homologous chromosomes?
chromosomes that have the same genes at the same loci; one maternal and one paternal
genome
genetic information, haploid set of chromosomes for a particular species
somatic cells
contain one set of chromosome from female parent and one homologous set from male parent
Haploid number?
n, the number of chromosomes in sex cells (n=23)
diploid number
2n, the total number of chromosomes in somatic cells (2n=46)
Name the 3 components of a chromosome
short arm (p)
centromere
long arm (q)
What are chromosomes except sex chromosomes called?
autosomes
What is a karyotype?
a pictures of a person’s chromosomes
mitosis
the process by which all somatic cells become descendants of one original cell. Original cell is divided into 2 daughter cells, producing exact copies
meiosis
process by which gametes cells are produced (egg and sperm)
2 consecutive cell divisions producing cells with half the original chromosome number
spermatogenesis
diploid primordial cells in testes become spermatogonia
oogenesis
diploid primordial ovaries become oogonia
What is codominance?
when 2 alleles for a trait are equally expressed (ex. AB blood type)
What is incomplete dominance?
heterozygotes have phenotypes that have both alleles visible as a blend (ex. wavy hair)
Penetrance
the probability that individuals in a population who have a particular gene combination will show the condition
Genetic marker
Sequence of DNA with a known location on a chromosome
Expression
the components of the phenotype that are exhibited in an individual (2 people with the same gene may express it differently)
Anticipation
genetic disease that increase in severity or have earlier onset with each generation (ex. Huntington)
What are balanced chromosomal abnormalities? Name the two types of balanced abnormalities
no net loss or gain of chromosomal material
Balanced translocation- ruptured chromosome, re-sticking in wrong combination
inversion- piece of chromosome flipped around and reinserted
Name the types of unbalanced chromosomal abnormalities
deletions
insertions
unbalanced translocation
Functions of 3 generation pedigree
Helps with:
- making a dx
- deciding on testing
- establishing pattern of inheritance
- identifying people at risk
- educating pt
- determining reproductive options
Describe the characteristics of autosomal dominant transmission
vertical pattern of transmission
multiple generations affected
variable expressivity
reduced penetrance
M/F equally affected
Autosomal Recessive
2 copies of diseased allele required for expressing the phenotype
rare
males and females equally affected
often occurs in the context of consanguinity
Describe the characteristics of autosomal recessive transmission
horizontal pattern
single generation affected
M/F equally
higher association with consanguinity
x-linked
no male to male transmission
males are usually more severely affected than females
“x-linked recessive” and “x-linked dominant” only apply to females
Multifactoral/complex disease
caused by interactions of variations in multiple genes and environmental factors
These genes make a person susceptible to a disorder and certain environmental factors trigger the susceptibility
Down syndrome
trisomy 21
most common chromosomal abnormality in live birth
increased incidence with advancing maternal age
What kind a testing can an expecting mother have to evaluate for down syndrome?
quad screening
nuchal translucency
What are the characteristics of down syndrome?
intellectual disability, characteristic facial appearance, increased social skills in childhood
some may have: cardiac defects, hearing loss, visual problems, GI defects, alzheimer disease in adulthood
trisomy 18
Edwards syndrome
many die before birth or in first month
inter uterine growth restriction. 2% 1 yr survival rate
increased risk with advanced maternal age
characteristics of trisomy 18
kidney and heart defects, developmental delay, club foot, low set ears, small jaw
trisomy 13
Patau syndrome
increased risk with advanced maternal age
characteristics of trisomy 13
severe intellectual disability, many physical abnormalities, cleft lip or palate, seizures, small jaw, polydactyly, heart defects, brain/spinal cord abnormalities
many children die within first days or weeks or life
Cri-du chat syndrome
deletion of part of short arm of chromosome 5
partial monosomy
can be detected in utero with chorionic vila sampling
define partial monosomy
when only a portion of a chromosome has one copy instead of two
characteristics of cri-du-chat syndrome
cat like cry of affected children due to abnormal larynx development, intellectual disability, wide set eyes, low ears
kleinflelter’s syndrome
Extra X chromosome, XXY
occurs during gametogenesis
affects male physical and cognitive development
accounts for many first trimester loses
characteristics of Klinefelter’s syndrome
physical traits become more apparent after puberty
hypogonadism, infertility, gynecomastia (breasts in man), reduced hair
turner syndrome
45 X, affects development in females
monosomy
characteristics of turner syndrome
non-functional ovaries, short stature, broad chest, webbed neck, amenorrhea, infertility, cardiovascular abnormalities
huntington’s disease
A neurodegenerative disease- progressive brain disorder that directly effects the nerves of the brain
autosomal dominant-only human disorder of complete dominance
adult onset: genetic defect is latent for 3-5 decades then manifests as progressive neuronal dysfunction
characteristics of huntington’s disease
causes uncontrolled movements, emotional problems, loss of thinking ability, changes in personality
early signs: depression, irritability, poor coordination, trouble learning
involuntary jerking movements associated with huntington’s disease?
chorea
Which chromosome is the huntington’s disease gene located? What does it code for?
chromosome 4
codes for a unique protein called huntingtin: CAG trinucleotide repeat
abnormal protein causes microscopic deposits of protein in neurons
Alzheimer’s disease
neurodegenerative disease, most common form of dementia in elderly
familial alzheimer’s disease
aka early onset AD
symptoms onset before 65
mutations on chromosomes 1, 14, or 21
rare, autosomal dominant
sporadic alzheimer’s disease
aka late onset AD
more common form
gene shown to increase risk: chromosome 19 apolipoprotein
definitive dx: autopsy-plaques and tangles
What are the 2 major breast cancer susceptible genes?
BRCA1 on chromosome 17 and BRCA2on chromosome 13 (tumor suppressor genes)
colorectal cancer
results from the interaction of both genetic and environmental factors
Familial adenomatous polyposis
<1% of all colorectal cancers
mutation in APC gene
cancer develops in 20s
recommended: total colectomy
Hereditary Nonpolyposis colorectal cancer (HNPCC)
aka lynch syndrome
autosomal dominant inheritance
mutation in one of the many genes that code for DNA repair
cancers occur in 30s and 40s
chronic myelogenous leukemia
myeloproliferative disorder
more common in men
genetic defect: translocation between chromosomes 9 and 22
Philadelphia chromosome (22): produces a protein that codes for an enzyme that causes too many stem cells to develop into WBCs
clinical presentation of chronic myelogenous leukemia
insidious onset, slow progression over months to years of infections, anemia, bleeding, fever, night sweats, fatigue
Hemophilia
bleeding disorders caused by mutations in genes that code for coagulation proteins
What mutation causes hemophilia?
mutation on F8 or F9 genes, located on the X chromosome
What is the pattern of inheritance for hemophilia?
X-linked recessive pattern
What are the clinical manifestations of hemophilia?
hemarthroses, bleeding into muscles and other soft tissues; prolonged bleeding or oozing of blood after injury or surgery
sickle cell disease
atypical hemoglobin molecules (hemoglobin S), crescent shape
clinical manifestations of sickle cell disease
anemia, infections, episodic pain, SOB, fatigue, delayed growth
mode of inheritance of sickle cell disease
autosomal recessive
cystic fibrosis genetic mutation
mutation in the CFTR gene(cystic fibrosis transmembrane conductance regulator)
mode of inheritance for cystic fibrosis
autosomal recessive
clinical manifestations for cystic fibrosis
thick, sticky mucous obstructing airways in lungs and ducts in pancreas
meconium ileus- newborn intestinal obstruction due to thick fecal waste products
What is the most common cause of morbidity associated with CF?
pulmonary disease
what is the primary test for cystic fibrosis dx?
sweat chloride test, defective chloride channel doesn’t allow chloride to be reabsorbed
marfan syndrome mode of inheritance?
autosomal dominant
mutation responsible for marfan syndrome
inherited mutation or a new mutation of the fibrillin-1 gene (FBN1) codes for connective tissue proteins
clinical manifestations of marfan syndrome
tall stature, long thin arms and legs, arm span wider than body height, scoliosis, hyperflexible joints, overcrowded teeth
dislocated lens of the eye, AA/dissection
Neurofibromatosis Type I
aka recklinghausen disease
autosomal dominant
mutation on NF1 gene on chromosome 17 (tumor supressor gene)
manifestations of neurofibromatosis Type I
growth of neurofibromas-benign tumors that grow on nerves of skin and brain, changes in skin pigmentation (cafe au lait spots)
What is the crowe sign seen in neurofibromatosis Type I?
axillary or inguinal freckles
Polycystic Kidney disease
clusters of fluid filled sacs in kidneys, affects ability to filter the blood properly, they can become enlarged and fail
clinical manifestations of polycystic kidney disease
HTN, back pain, hematuria, UTIs, kidney stones
What are the two types of polycystic kidney disease?
autosomal dominant- sxs in adults
autosomal recessive-rare, lethal
What is done during a newborn screening?
biochemical analysis that determines whether certain proteins are present or absent, checks for metabolic disorders
when are the 2 tests for newborn screening performed?
1st: heel stick at 24-36 hrs
2nd: first office visit between 5-10days