Genetics Flashcards
1
Q
what are genes
A
hereditary units of DNA transmitted from one generation to another, basically they are codes for the production of proteins
2
Q
what is a Locus
what is an allele
A
the specific location of a gene on a chromosome
alleles are different versions of. a gene
3
Q
human alleles
A
humans have 2 alleles for each autosomal gene
4
Q
chromosomes
A
structure composes of genes located in the nucleus of a cell
they are distinguished from each other by length and the position of the centromere
5
Q
homologous chromosomes
A
have the same genes on the same loci one is maternal and one is paternal
6
Q
hw many chromosomes do human somatic cells have
A
46 total chromosomes made of 23 pairs
23 from mom23 from dad
7
Q
mutations
A
can be spontaneous or induced by exposure to mutagenic chemicals or radiation
the effects vary and depend on where in the gene code the mutation has occurred
8
Q
net result of a mutation
A
can be a physical. appearance or some other trait, again depending on the location
9
Q
allosome pair
A
the sex chromosome pair, all other 22 pairs are autosome chromomosemes
10
Q
p arm, r arm
A
in human chromosomes the short are is the p arm and the long arm is the q arm
11
Q
what determines maleness
A
genetic factors on the Y allosome
12
Q
mitosis involves which cells
A
somatic, creates an exact copy through division creates two daughter cells
13
Q
meiosis
A
produced gametes have 23 new chromosome pairs with new combos of the original maternal and paternal copies
only occurs in germ cells in the gonads
consist of two consecutive cell divisions producing cells with half he number diploid to haploid
14
Q
co dominance example
A
when two alleles for a trait are equally expressed AB blood type
an allele lacks complete dominant and restive relationships and both are observed
15
Q
incomplete dominance
A
heterozygotes have phenotypes that have both alleles visible as a blend
creates a third phenotype
human ex- wavy hair, skin color
16
Q
penetrance
A
probability that individuals in a population who have a particular gene combination will show the condition
17
Q
functions of 3 generation pedigree
A
Making a diagnosis Deciding on testing strategies Establishing the pattern of inheritance Identifying people at risk Educating the patient Determining reproductive options
18
Q
pedigree language
A
male square female circle
Diagonal line through symbol – deceased Shaded symbol – affected with trait
Half-shaded symbol – carrier of trait
19
Q
Consultand
A
The person seeking genetic advice
Can be healthy or a person with a condition
20
Q
proband
A
the affected individual
21
Q
autosomal dominant
A
65% of human monogenic disorders
mutations at just a single allele can cause a disease in an individual
22
Q
autosomal dominant example
A
Huntington’s disease
23
Q
characteristics of Autosomal Dominant disorders
A
vertical pattern multiple generations are affected
expressivity may be variable
some with the makeup may not show the phone type
males and females equal
male to male transmission seen
24
Q
autosomal recessive
A
25% of human monogenic disorders
tend to envolve enzymes or receptors
rare
often seen in consanguinity
25
autosomal recessive example
cystic fibrosis
26
x linked
5% of human monogenic disorders
males more likely to develop both D and R
D and R only apply to females
all daughters of an affected male are heterozygous carriers
males usually more severely affected than females
27
x linked heterozygous females usually are
normal or mild
28
x linked male to male transfer
is not possible
| unaffected makes do not transmit the phenotype
29
x linked dominant examples
aport's syndrome, fragile X syndrome
30
x linked recessive example
wiskott aldrich syndrome
| Duchenne muscular dystrophy
31
Multifactorial/Complex Disease examples
```
Cancer
Diabetes
Asthma
Heart disease
Mental illness
Cleft lip/cleft palate
```
need an environmentally factor to turn on gene, meet threshold for phenotype to show
32
Down syndrome
trisomy 21, most common chromosomal abnormally in live births
gamut has two copies of chromosome 21
leads to trisomy when it is fertilized
1 in 500 pregnancies
33
pre natal testing for Down syndrome
quad screen and nuchal translucency
34
what else can cause Down syndrome
4% f cases are due to roberystonian translation, this would require us to do parental chromosome studies
35
Down syndrome characteristics
intellectual disability, facial appearance, 40% cardiac defects 75% hearing loss less than 50% have visual problems and 7% have GI defects
increased social skills in childhood
36
Edwards syndrome
trisomy 18, second most common autosomal trisomy that goes to full term
translocation can cause this disorder
many will die before birth or first month
1:5000 live births
IUGR
highly lethal in utero 85% are lost between week 10 to term
50% die in first week of life
2% 1 year survival rate
heart go and kidney defects
37
Edwards syndrome characteristics
kidney and. heart defects, developmental delays club foot rocker bottom feet
low set ears small jaw
38
patau syndrome
```
trisomy 13
1:16000 live births
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 of life
```
39
patau syndrome and translocation
Some caused by Robertsonian translocation involving chromosomes 13 and 14
When a part of chromosome 13 gets attached to chromosome 14 during formation of gametes
Affected people have 2 normal copies of 13 plus an extra copy attached to another chromosome
40
Cri-du-Chat Syndrome
chromosomal abnormality deletion of part of short arm on chormose 5
Cat-like cry of affected children due to abnormal larynx development
Intellectual disability, wide set eyes, low ears
1 in 50,000 births
Can be detected in utero with CVS
41
Klinefelter’s Syndrome
Extra X chromosome, 47 XXY
Occurs during gametogenesis
Affects male physical and cognitive development
Accounts for many first trimester losses
Physical traits become more apparent after puberty
Most common sex chromosome aneuploidy in males
Hypogonadism, infertility
Gynecomastia, reduced hair
42
Turners syndrom
```
45 X, affects development in females
Gonadal dysgenesis
Non-functional ovaries
Short stature
Broad chest
Webbed neck
Amenorrhea
Infertility
Cardiovascular abnormalities
```
43
Huntington’s Disease
A neurodegenerative disease
Causes uncontrolled movements, emotional problems, and loss of thinking ability, changes in personality
Early signs: depression, irritability, poor coordination, trouble learning
chorea
Adult onset: genetic defect is latent for 3-5 decades, then manifests as progressive neuronal dysfunction
44
Huntington’s Disease Pathophysiology
HD gene on chromosome 4 that codes for a unique protein called huntingtin
CAG trinucleotide repeat
Normal: 10-35 repeats
In HD: 36-120 repeats
causes microscopic deposits of protein in neurons
Average time from symptom onset to death is 15 years
45
Huntington’s Disease inheritance
Only human disorder of complete dominance
| Heterozygotes are just as affected clinically as homozygotes
46
Alzheimer’s Disease
A neurodegenerative disease
Most common form of dementia in older individuals
Usually begins after age 60; risk increases with age
Death usually occurs within 10 years
People with parent, sibling, or child with AD are at increased risk
Progressive mental deterioration: memory loss, confusion,
disorientation
47
dementia forms
65% from Alzheimer’s Disease
| 35% vascular in nature
48
Alzheimer’s Disease Pathophysiology
loss of acetylcholine causes Formation of plaques and tangles
Atrophy of brain
Resultant effect – blocked communication
Several gene mutations cause predisposition to AD
49
Alzheimer's late vs early onset
familial early onset
| sporadic late onset
50
early onset
```
Many members of multiple generations affected
Symptoms start before age 65
Mutations on chromosomes 1, 14, or 21
Induce formation of a “sticky” protein
Rare - <5% of cases of AD
Autosomal dominant
```
51
Sporadic Alzheimer’s Disease
One gene has been shown to increase risk
Chromosome 19 apolipoprotein E (APOE) gene Not everyone carrying the gene develops disease
Definitive diagnosis: autopsy-plaques and tangles
52
Hereditary Breast and Ovarian Cancer Syndrome risk factors
gender age and family history
| up to 10% of breast and ovarian cancers are caused by known predisposing genetic factors
53
Hereditary Breast and Ovarian Cancer Syndrome Genetic testing
Preferable to first test an individual who is affected by cancer before testing unaffected family members
Helps to identify whether a detectable BRCA1 or BRCA2
An individual can inherit a BRCA1 or BRCA2 mutation yet never develop cancer
54
colorectal cancer
Genetic predisposition is the main risk factor in only a small proportion of people
Diet, exercise, smoking, obesity are stronger risk factors in most people
55
familial colorectal cancers
Patterns within a family that exist without identifying a specific mutation
A family history of one or more people with colorectal cancer or premalignant polyps
56
familial colorectal cancers may be due to
Chance alone
Shared exposure to a carcinogen or diet/lifestyle factors
Combination of gene mutations and environmental risk factors
57
Familial adenomatous polyposis (FAP)
autosomal dominat
genetic mutation at APC (adenomatous
polyposis coli) gene
polyps in colon begin forming in adolescence
APC is a tumor suppressor gene on chromosome 5
when it is mutated it allows for cancers to develop in 20s
risk of developing colorectal cancer is near 100% usually before age 50
Time from polyp to cancer development is 10+ years
58
genetic cosseting and testing for FAP
should be offered to all patients with suspected diagnosis of FAP after colonoscopy and to relatives at risk
children should have the screening by 10 years of age
59
recommendation for those with established FAP
total colectomy before age 20
60
hereditary nonpolyposis colorectal cancer
HNPCC / Lynch syndrome
2-3% all colorectal cancers
autosomal dominant
mutation in many genes that code for DNA repair
more rapid transition from adenoma to cancer than FAP
cancers occur earlier 30 and 40s
can occur with small number or no polyps present
associated with formation of other cancers such at uterus ovaries stomach UT small bowl and bile ducts
61
hereditary nonpolyposis colorectal cancer men vs women
50% chance of cancer in women and 70% in men
62
genetic testing HNPCC
if mutation is found
it is recommended that regular colonoscopy start at age 25 for relatives or 5 years younger than the youngest that those diagnosed
upper endoscopy every two years to screen for gastric cancer
screening for endometrial and vain cancer in women at age 25 to 35
63
chronic myelogenous leukemia
myeloproliferative disorder (blood cancer)
more common in men
55 years old median age for presentation
translocation between chromosomes 9 and 22
64
Philadelphia chromosome
chromosome 22
| produces a protein that codes doe an enzyme that causes too many stem cells to develop into WBCs
65
chronic myelogenous leukemia pathophysiology
increased production of abnormal white blood cells that are none functional and take up bone marrow space that is meant for WBC RBC and platelets
66
chronic myelogenous leukemia clinical presentation
insidious onset slow progression over months or years
| infection anemia bleeding fever night sweat fatigue
67
chronic myelogenous leukemia diagnosis
bone marrow aspiration for karyotype
68
hemophilia
bleeding disorder cause by mutation in genes that code for coagulations proteins
mutations on F8 or F9 on the X sex chromosome
x linked recessive
69
hemophilia mutations (2)
F8 causes VIII deficiency causing the more common hemophilia A
F9 causes IX deficiency causing hemophilia B or Christmas disease
70
hemophilia clinal manifestations
hemarthrosis, bleeding into muscle and soft tissue, prolonged bleeding or oozing
severity is variable
71
sickle cell disease pathophysiology
atypical hemoglobin molecules (S) distorts red blood cells in to present or sickle shape causing RBC to break down prematurely
the mutation occurs on HBB gene
72
sickle cell disease clinical manifestations
anemia, infections, episodic pain, SOB, fatigue delayed growth
73
sickle cell disease
autosomal recessive
| more common in people whose ancestors came from Greece Africa turkey Italy
74
cystic fibrosis
```
autosomal recessive
mutation in the CFTR (regulator) gene
this gene codes for a protein that regulates chloride channels in epithelial cells
when it is mutated the protein is defective and there is a disruption in the chloride and water transport and water balance in secretions is disrupted
common in white population in the US
1 3500 white newborns
1 in 25 are carriers
diagnosed by age 1
```
75
cystic fibrosis clinical manifestations
Causes thick, sticky mucous obstructing airways in lungs and
ducts in pancreas
difficult breathing, infections in lungs
76
cystic fibrosis Problems with nutrient digestion
Buildup of mucous prevents pancreatic enzymes from reaching intestine
Failure to thrive, poor growth rate
Meconium ileus – newborn intestinal obstruction due to thick
fecal waste products
77
most common morbidity associated with CF
pulmonary disease
Pulmonary system can’t defend against pathogens well – leads to sinusitis and bronchitis
Most common organisms: S. aureus, P. aeruginosa, Aspergillus Nasal polyps, nosebleeds, chronic sinus infections common in
CF patients
Thick mucous builds up in lower airways causing obstruction
78
sweat chloride test
primary test for CF diagnosis
Defective chloride channel doesn’t allow chloride to be
reabsorbed
Concentration of chloride in sweat is elevated in CF
Genetic testing used to confirm results
79
marfans syndrome
autosomal dominant
inherited muslin or a new mutation of the fibrillar -1 gene
defects are seen in the connective tissue of bones ligaments muscles blood vessels and heart valves
80
marfans syndrome clinical manifestations
```
tall stature
arm span wider than body height
long narrow face
high arched palate
over crowed teeth
scoliosis
hyperflexible joints
chest deformities
```
81
marfans syndrome key featurs
dislocation of the lens of the eye
aortic aneurysm and dissection
heart defects are major causes of morbidity and morality
mitral valve prolapse and aortic valve regulation
= SOB fatigue palpitations
82
those with marfans should avoid contact with
sports caffeine and decongestants due to increased stress placed on CV system
83
Neurofibromatosis Type I
Von Recklinghausen disease, autosomal dominant
mutation on NF1 gne on chromosome 17, most common
a tumor suppressor gene
results in growth of neurofibromas and skin pigmentation changes cafe au last spots
lisch nodules in iris
freckles in axillae and groin
84
neurofibromas
benign tumors that grow on nerves of skin and brain
| 2 or more for diagnosis of Neurofibromatosis Type I
85
Crowe sign
axillary or inguinal frecking
86
neurofibromas diagnostic features
1.5 cm or larger café-au-lait spot post puberty or 6 or more café-au-lait spots 0.5 cm or larger in before puberty
2 or more neurofibromas
Axillary or inguinal freckling (Crowe sign)
Optic glioma
2 or more Lisch nodules
1st degree relative with NF1
87
polycystic kidney disease
Clusters of fluid filled sacs develop in kidneys, this affects ability to filter the blood properly. kidneys become enlarged and can fail
88
polycystic kidney disease clinical manifestations
hypertension, back pain, hematuria, UTIS kidney stones
89
polycystic kidney disease other associations
liver cysts, heart valve abnormalities, increased aortic aneurysm and brain aneurysm
90
polycystic kidney disease forms
Autosomal dominant – sx start in adulthood 1 in 1000; PKD1 and PKD2 genes
Usually inherited (90% of the time)
Autosomal recessive – rare, lethal early in life 1 in 30,000
PKHD1 gene
91
Approximately _____% of all newborns have some birth defect
10%
Ranges from minor biochemical problem to severe physical deformity
Caused by variety of biological, chemical, and physical agents
Contributors: mutant genes, chromosomal defects, multifactorial components
92
biggest cause of birth defects
unknown etiology
93
Teratology
study of abnormal development
94
Teratogens
nything capable of disrupting embryonic or
| fetal development and producing malformations
95
critical period for
teratogenic effects is 3-16 weeks
| timing of exposure determines which systems are affected
96
CNS development vs teeth and palate development in utero
CNS begins to develop in 3rd week, while teeth and palate begin to form in 6th-7th week
97
new born screening
Biochemical analysis that determines whether certain proteins (enzymes) are present or absent
typically autosomal recessive conditions
“inborn errors of metabolism”
Inherited defect in one or more enzymes
law 2008 increased uniform testing
first test at 24-36 hours old next at 5 to 10 days
