human genetics test final Flashcards
how do you figure out an incest child having the disease?
pathway tracingg
what is pathway tracing?
following the allele away from the known location and moving away from the reference point and toward the point in question
what is a primary relative?
immediate relative (just one position away along a descent line)
what is a secondary relative?
slightly removed ( two positions away)
what is a tertiary relative?
more distant relative (3 positions away)
are there fourth degree relatives?
yes, but we donﾒt go out that far
def of multifactorial inheritance
genetics is due to many factors, some genetic some not
two fundamental forms of multifactorial inheritance?
multiple genes determine trait (polygenic inheritance), and a single gene and enviromental factors
what are the early cases of multifactorial inheritance?
penetrance, variable expressivity
what is the example of polygenic inheritance used?
wheat grain color
what do you begin to see if one begins to put the phenotypes on a graph?
normal distribution (bell curve)
what color of wheat is most common?
pink (amber as he says it)
what else seems to work in the same way as wheat color?
human skin color
what determines the higher continuous variation?
the greater the number of genes involved in the polygenic system
what happens if you add in chances for additional enviromental variables to a polygenic system?
the variation becomes very smooth and continuous, and therefore it becomes very difficult to dissect out the genetic component
what is the genetics of obesity?
complex multifactorial trait
what are the factors of obesity?
a trait where you wont get saitity, and the enviromental is where you over eat and not exercise
what is the genetics of intelligence?
complex multifactorial trait
what did the Bach pedigree look like?
it LOOKED like musical genius was a autosominal dominant trait
is the use of a pedigree a good way to be used as convincing evidence for a complex mulifactorial trait?
it may be problematic
what should you use instead?
comparing specific genotypes placed in differing or same enviroments
what is an example of genotypes living in different enviroments?
monozygous twins that have lived in different enviroments
what are the results of the monozygous twin studies?
the twins yeild substantial evidence for a GENETIC basis to intelligence
what university has an ongoing monozygous twin study?
university of minnesota
what is the final conclusion of the twin studies?
merely confirm that both genetic and enviromental factors are important, although many would argue that its evidence for genetic factors
what is another way to approach mulitfactorial inheritence? (other than pedigree or genetic cohort)
heritability
def of heritability
an estimate of the population phenotypic VARIATION that is due to genotype
another def of heritabilityﾅ.
the fraction of the phenotypic variability in the population which is determined entirely by genotype
heritability = 1
the population phenotypic variance is likely due entirely to genotype
heritability = 0
the population phenotypic variance is likely due entirely to enviroment
what does heritability a measure of?
correlation between genotype and phenotype
what does inheritance tell us?
the HOW of a trait
what does heritability tell us?
how MUCH (genetic predisposition)
how is heritability looked at in the final analysis?
abstraction of limited value for routine inheritance prediction or understanding specific genetic factors
what is the newest way to approach multifactorial inheritance?
find the correlation b/t some specific DNA marker sequence found in 2 populations, one with trait one w/o
what have single nucleotide polymorphisms done?
proven to be helpful to identify genes for a susceptibility to the development of a disease
what are empirical risk figures?
a gathering of observational studies that might be used to predict the future based on the past
what do empirical risk figures give you?
only provide data based on similar prior situations, not anything b/t genetic or enviromental
what are the common ways to approach multifactorial inheritance?
pedigrees, twin studies, heritability, DNA associated studies, empirical risk tables
pro/ con pedigree
attemping to model the disease- but not good except for finding broad patterns
pro/con twin studies
difficult to use in practical way
pro/con heritability
complex mathematical derivation and of limited practical use
pro/con DNA associated studies
requiring difficult laboratory testing and only susceptibilities
pro/con empirical risk table
requires large statistical databases and do not explain mechanisms
familial risk compared to gen pub?
considerably higher
familial risk over generations?
drops sharply with increasing distance to index case
what is the risk of a first degree relative?
roughly a square root of the population risk
what is higher when more than one family member is affected?
recurrent risk
what are the two basic ways to look at human multifactorial traits?
1)model the disease 2)develop empirical risk figures
how do you model the human multifactorial trait?
look for a basic pattern of inheritance using a pedigree, then develop rules, as needed, for deviation from simple predictions
how do you use the empirical risk figures to look at a human multifactorial trait?
rely on PRIOR OBSERVATIONS to est statistical tools of prediction
def of adolescent idiopathic scoliosis (AIS)
multifactorial condition of spinal curvature laterally >10 degrees
how common is AIS
1 in 30 in persons 10-16 years of age
how does the pedigree of AIS look?
autosomal dominant with reduced penetrance
what is the penetrance of AIS?
~60%
how do you find the penetrance of AIS?
from one parent, a simple autosomal dominant model would have to have generated a recurrent risk of 50% and yet the statistic is 29% so 0.5x0.6=0.3 so 60% penetrance
def of spondylolysis/ spondylolisthesis
multifactorial conditions of spinal pars interacticularis and a common source of low back pain
spondylolysis=
a stress fracture of the pars of the vertebral body
spondylolithesis=
a slippage of vertebral bodies which may happen due to spondylolsis or degenerative changes with age
how common are spondylolysis?
~5% of pop
how common are spondylolithesis?
~2.5%
what is the general pedigree look of spondys?
autosomal dominant with reduced penetrance
what is the penetrance of spondys?
~40%
def of congental dislocation of the hip?
(acetabular dysplasia) multifactorial anomaly characterized by displacement of the femoral head outside of acetabulum prior to birth
how common is hip dislocation?
1 in 1000 births
what model does hip dislocation follow?
autosomal dominant with reduced penetrance
what is the recurrence risk for sibs in congenital dislocation of the hip?
about 5%
what is ankylosing spondylitis?
multifactorial autoimmune “spondyloarthropathy” condition. Chronic painful progressive inflammatory arthritis primarily affecting spine and si jts
what antigen is ankylosing spondylitis correlated to?
HLA- B27
how common is AS
1 in 400
neural tube defects (including spina bifida)
multifactorial condition characterized as an embryonic failure to fully close the developing neural tube
what chomosomes are neural tube defects linked to?
17q11 and 6q27
how common are neural tube defects?
1 in 1000
what is the recurrence risk for sibs in neural tube defects?
~4%
pyloric stenosis?
multifactorial anomaly of substantial narrowing of the stomach pylorus, where there is hypertrophy and hyperplasia of the pylorus
incidence of pyloric stenosis?
1/400 m>f so SEX INFLUENCED
what pattern does pyloric stenosis follow?
autosomal dominant with reduced penetrance with some sort of sex influence
cleft lip and palate?
multifactorial anomalies with a development failure of fusion of the frontal process with the maxillary process during embryonic development
incidence of cleft lip/palate?
1 in 700
pattern does cleft lip/palate follow?
autsomal dominant with variable expressivity/ severity
club foot?
multifactorial collection of congenital anomalies characterized by a foot that is twisted in and down
what are the skeletal deformities with club foot?
TALIPES EQUINAVARUS, talipes calcaneovalgus, metatarsus varus
def of talepes equinavarus?
adduction of the forefoot, inversion of the heel and plantar flexion of the forefoot and ankle
incidence of club foot
3 in 1000
pedigree pattern of club foot>
autosomal dominant with reduced penetrance
pentrance of club foot?
40.00%
diabetes
multifactorial condition of abnormal glucose metabolism/ utilization characterized by hyperglycemia, due to altered insulin secretion from the pancreatic beta cells or receptivity to insulin
what types of diabetes are clinically similar to diabetes with hyperglycemia?
glucosuria, polyuria, and polydispsia
which of the two diabetes has a higher genetic link?
type 2
what is the sibship risk of diabetes?
~40%
what is the risk of a child of a parent with type 2 diabetes?
33.00%
hypertension?
multifactorial condition characterized by high systemic arterial blood pressure, which is a physial finding which may have many causes
what are the 3 genetic characteristics that all biological populations have?
1)a gene pool 2) allelic frequencies 3) genotypic and phenotypic frequencies
what is a gene pool?
the sum total of all the alleles in the reproductive gametes from members of a mendelian population; the raw material used to build a subsequent generations
what is a mendelian population?
a group of diploid, sexually interbreeding (or potentially interbreeding) individuals possessing a common gene pool
what does gene pool mathematical modeling require?
the hardy-weinberg equilibrium
what is the hardy-weinberg equilibrium?
that a pool be in a special balanced state wherein allelic frequencies remain constant
what are the 5 conditions that must be constant to get a H-W equilibrium
1) no mutation 2)no migration 3) no assortive mating 4) no selection 5) no genetic drift
what is the “A” FREQUENCY?
p
what is the “a” FREQUENCY?
q
what does p+q= ?
1 (or 100% of the variation of the gene in question)
what are the letters for 3 allelic forms?
p+q+r= 1
what are the letters for 4 allelic forms?
p+q+r+s=1
what are the letters for homozygous dominants (AA)
p^2
what are the letters for heterozygotes (Aa)
2pq
what are the letters for homozygous recessives (aa)
q^2
in a 2-allelic system, what is the formula for the frequency of genotypes in this population?
p^2 + 2pq + q^2 = 1
what is the formula for a 3 allelic system?
(p+q+r)^2 = 1
what is the formula for a 4 allelic system?
(p+q+r+s)^2 = 1
what are the blood types caused by?
glycosphinglolipids produding from the plasma membrane of the RBC
what the ABO systema an example of?
a multi-allelic gene on chromosome 9
what is erythroblastosis fetalis?
incompatibility b/t maternal and fetal blood leading to fetal loss
what is the major histocompatibility complex?
larger cluster of genes on chromosome 6 that determine whether or not transplanted tissues will be rejected
what does the major histocompatibiliy complex code for?
the production of human leukocyte antigen (HLA)
what are the functions of HLA type 1?
important on all cells in establishing one’s self
what are the functions of HLA type 2?
know to be imporant in the presentation of foreign antigens to the immune system
def of haplotypes
a combination of alleles (for different genes) that are located closely together on the same chromosome and that tend to be inherited together
do HLA allelic formations cause disease?
particular HLA allelic forms have been correlated with particular diseases
what is the risk for anylosing spondylitis with people that have HLA antigen B27?
over 90 times greater than the normal population
what is an antibody?
a protein coded for by a gene, though it is a rather complex example of gene expression
what is severe combined immunodeficiency (SCID)
a collection of disorders characterized by a loss of immunoglobulin production, both t and b lymphocytes are crippled
what is agammaglobulinemia?
Heterozygous collection of disorders involving a lack of plasma cells and no immunoglobulin production
how do infectous agents gain “access” to the human body/ cells?
by having evolved to bind to specific cell surface molecules, coded for by genes
can some cancer types run in families?
yes
what is cancer ultimately a disease of?
genes
what are proto-oncogenes?
promote cell division in many forms
what are the forms that proto-oncogenes can promote cell division?
1)growth hormone r/c 2) G- protein transducers 3) transcription promoters
what are the mutated proto-oncogenes called?
oncogenes
what do oncogenes do?
promote uncontrolled cell division
what are most ongenic mutations considered as?
dominant (bacause a single copy being inappropriately switched on will create a problem)
what is burkitts lymphoma?
rare cx of the lymph organs most often due to a TRANSLOCATION b/t chromosomes 8 and 14
what is chronic myelogenous leukemia?
rare cx, though a common form of leukemia that is due to TRANSLOCATION b/t chromosomes 9 and 22
what is the Philedelphia chromosome?
translocation of 9 and 22
what are tumor suppressor genes?
inhibit cell division
what are the best described tumor suppressor genes?
Rb for retinoblastoma; BRCA1 and p53
how common is p53?
active in ~50% of all cx
what was the gene on the year in 1995?
p53
where is p53 found?
chromosome 17
what does the knudson hypothesis state?
carcinogenesis requires multiple mutations
what is kundsons other model?
the two hit model
what is the two hit model?
a model that may explain many cxs that mainly involve tumor-suppressor genes
what needs to happen in the two step model?
1)both copies of a tumor-suppressor need to be mutated (sporadic cx) 2) if only one mutant gene is inherited, then it would only take a single hit to lose tumor-suppression (familial cx)
what makes the cx cell exceed the normal number of mitotic cycles?
activation of the gene for telomerase seems to make this possible
what is the function of telomerase?
enzyme lengthens the chromosomal telomeres
how are most cxs classified as? Classically inherited or not?
most are not classically inherited (sporatic) but some can be considered classic
what type (sporatic or classic) are most breast and colon cxs?
most are sporatic (hereditary makes up 5%)
a person with BRCA1 or 2 have what risk of getting breast cx?
~60-80% risk
carcinogenesis requires what?
multiple damages to cell cycle controlling genes
what ways can oncogenes cause cx?
1)direct mutation 2) virus promotion (15%) 3) chromosome rearragement
what ways can switching off tumor-suppressor gene cause cx?
direct mutation
why is cx a multifactorial condition?
because there are genes and enviromental agents involved as well as cx is a collection of diseases, there is no simple risk assessment for all forms
how many base pairs does mitochondria have?
~17000 base pairs which codes for 40 genes
what makes the mitochondria cx predictions so difficult?
reproduction of mitochondria is unpredicable and there can be hundreds of them in a given cell (all with different mutations)
what gamete passes on the mitochondria?
ONLY the mitochondria of the OOCYTE are thought to be transferred to the next generation
what diseases have been confirmed to be mitochondrial in origin?
1) leber’s Optic Neuropathy 2)kearns-sayre 3)Leighs syndrome 4) myoclonic epilepsy with ragged red fibers 5)NARP
what is Lebers hereditary optic neuropathy?
mitochondrial disorder characterized by mid-life onset of acute or subacute, painless, CENTRAL vision loss
what is Kearns-Sayre Syndrome?
Mitochondrial disorder characterized by opthalmoplegia, retinal pigment degeneration, and cardiomyopathy
what is leighs syndrome?
mitochondrial disorder, with early onset of neuropathy consisting of focal, bilateral lesions in one or more areas of the CNS
*myoclonic epilepsy with ragged red fibers?
*Mitochondrial disorder, with multisystem weakness, and myoclonus as first symptom, then epilepsy, then weakness and dementia
what is NARP?
Neurogenic weakness, Ataxia, and Retinitis Pigmentosa; mitochondrial disorder, with variable combination of developemental delay,
how did scientists trace back to a “kind of eve” or a mother to all living people?
with looking at mitochondrial DNA and how it mutates in a sort of molecular clock
is there diversity in the ability of a person to process or metabolize nutrients?
yes
is there evidence that nutrients can alter gene expression?
yes
can nutrients take away functions that genes would otherwise have to do?
yes nutrition can affect other metabolic pathways
do nutrients represent nature or nurture?
nurture
what is genetic counseling?
process by which patients at risk for a genetic disease are advised of the nature, risk and consquences of having or producing an affected child/relative
what does genetic counseling involve?
a collaborated effort b/t health professionals
how does almost all of the genetic counsiling start?
with a pedigree
what is duputytrens contracture?
a Fascia closure of the hand that is not always evident until mid-life.
how is deuputytrens contracture passed?
autosomal dominant
what is Cystic Fibrosis?
a metabolic failure of chloride ion transport across membranes
how is cystic fibrosis passed?
autsomal recessive
what is congenital dislocation of the hip syndrome?
relatively benign skeletal anomaly
hos is Congenital dislocation of the hip passed?
multifactorial
what is the most common quesiton in genetic counseling scenarios?
what is the chance that we might have another affected child? (recurrent risk)
what is the recurrent risk for an autosomal recessive disorder?
25.00%
what is the recurrent risk for an autosomal dominanit disorder?
50.00%
what is the recurrent risk for a rare, sex linked recessive?
25% overall (50% for male 0% female)
what is the recurrent risk for trisomies of autosomes?
slight increase over the normal population of the same age
what is the recurrent risk for a multifactorial inheritance?
usually less than 10% but often requires use of an empirical risk table
what are the two bolded questions that we need to know for genetic counseling for information?
1) what is the exact diagnosis 2) what aare the known facts and results of an examination of a family history
what is considered convential practice when it comes to genetic counseling?
refer
what are the red flags that should prompt a consideration of a genetic causality?
Family GENES
what does F GENES stand for?
Family history; Groups of congenital abnormalities; Extreme/ exceptional presentation, Neurodevelopemental delay, Extreme or exceptional pathology, Surprising lab values
what is the leading indication for prenatal diagnosis?
late maternal age
what are the other reasons for prenatal diagnosis and counseling?
1)prior child with it 2) prior history of miscarriage 3) known chromosomal defects in one of the parents 4) Family history 5)specific ethnic high-risk
what are some of the therapies that might be able to help get rid of many genetic dzs in the womb?
blocking or enhancing cellular function at transcription, translation or post-translation
