1M - Genetics Flashcards
study of genes, heredity, and the variation of the inherited characteristics
Genetics
deals with the etiology and pathogenesis of human diseases that are at least partially genetic in origin, along with their prediction and prevention
medical genetics
study of gene function and interaction
genomics
how many percent of individuals is diagnosed with a genetic defect by age 15?
3%
2-3% newborns
8-10% by age 18, have one or more functional or developmental characteristics
biochemical gene marker for breast cancer?
BRCA 1 and 2
Which project identified more than 25,000 human genes which led to a rapid expansion of genomic research to better understand disease biology
Human Genome Project 2003
Genetic code varies every 200-500 base pairs usually as?
SNP (single nucleotide polymorphism)
How many single nucleotide polymorphism does the human genome have?
more than 80
Aneuploidy accounts for how many percent of 2nd trimester miscarriages?
20%
> 50% of 1st trimester miscarriages
6-8% of stillbirths and early childhood deaths
Trisomy 21`
Down Syndrome - 50% of aneuploidy cases
Trisomy 18
Edward - 15% of aneuploidy cases
Trisomy 12
Patau - 5% of aneuploidy cases
p in chromosome nomenclature stands for?
Short arm
q in chromosome nomenclature stands for?
long arm
nomenclature for trisomy 21 in a genetic male
47, XY, +21
Nomenclature for Klinefelter syndrome
47, XXY
Nomenclature for Turner Syndrome
45, X or 45, XO
How many chromosomes are there in a euploid?
46
how many chromosomes are there in a aneuploid?
gain or loss from 46
a polyploid chromosome has?
a multiple of haploid 23 e.g. 69
half of all chromosomal abnormalities?
Autosomal trisomy
Trisomy most commonly results from?
Non disjunction
How does non disjunction happen?
Failure to pair up
pairs up but separates prematurely
fail to separate
risk for any autosomal trisomy is greatly increased after reaching what maternal age?
35
From birth tilll ovulation the oocytes are suspended in what phase of meiosis?
Mid prophase of meiosis I
If non disjunction happens, the gamete which receives the affected chromosome when fertilized, results in?
Trisomy
the gamete that receives no copy, when fertilized results in monosomy
Aneuploidy is higher in sperm or oocytes?
oocytes
Oocyte vs sperm (10-20% vs 3-4 %)
after pregnancy with a trisomy, what is the risk of having another trisomy in future pregnancy?
1%
What procedures are ordered during pregnancies with history of trisomy?
Chorionic Villus sampling and amniocentesis
If there is history of pregnancy with unbalanced translocation or structural rearrangement. what procedure may be ordered for the parents?
parenteral chromosomal studies
most common non lethal trisomy
Down Syndrome
how many percent of fetal death rate beyond 20 weeks of gestation is caused by down syndrome
5%
Most common cause of trisomy 21? non disjunction, robertsonian translocation or Mosaicism?
Non disjunction - 75%
Robertsonian Translocation - 3-4 %
Mosaicisim - 1-2%
75% of cases of non disjunction happens during meiosis I or meiosis II?
Meiosis I
25% during meiosis II
Adult women with Down Syndrome are fertile or sterile?
fertile
Male with down syndrome are sterile
How many percent of the offspring of women with down syndrome will also have down syndrome?
33%
What particular cardiac defects may affect 50% of liveborn neonates with Down syndrome?
Ventricular septal defects and endocardial cushion defect
Those with down syndrome are more at risk of what GI defects?
Esophageal atresia
hisrschsprung disease
duodenal atresia
What are the characteristic features of those with Down Syndrome?
brachycephaly
Epicanthal folds with upslanting palpebral fissure
brushfield spots (grayish spots on the periphery of the iris), flat nasal bridge and hypotonia
infants with loose skin along the nape
single palmar crease
sandal toe sign
hypoplasia of the middle phalanx of the 5th finger
Prognostic health problems for those with Down Syndrome?
Hearing loss Severe optical refractive errors cataracts Obstructive sleep apnea thyroid diseases leukemia
Degree of mental impairment?
Mild to moderate
Average IQ of those with down syndrome
35-70
Social skills of those affected with down syndrome are higher than predicted by their IQ scores. True of False?
True
What is the 10 year survival rate of those with Down Syndrome?
at least 90%
99% for those without major malformations
What is the 1 year survival rate of Edward Syndrome?
2%
Edward syndrome is recognized 1 in 2000 pregnancies while only 1 in 6600 liveborn neonates. The reason for being less recognized in liveborn neonates is caused by?
High in utero lethality and termination of affected pregnancies
more than half die within the first week
what organ system is affected by Edward Syndrome?
Virtually every organ system
Common major anomalies found among those with Edward Syndrome
VSD cerebellar vermian agenesis myelomeningocele diaphragmatic hernia, omphalocele, imperforated anus horseshoe kidney
Cranial and extremity abnormalities among those with Edward syndrome
Prominent occiput posteriorly rotated and malformed ears micrognathia clenched hands with overlapping digits radial aplasia with hyperflexion of the wrist rocker bottom feet with clubbing
A strawberry shaped cranium is noted among 40% of cases of Edward Syndrome. What causes this?
Abnormally wide cavum septum pellucidum and choroid plexus cyst
If pregnancy with Edward Syndrome progresses until the third trimester? What is the common fetal complication
Fetal growth restriction with mean birth weight of less than 2,500g
Trisomy 13 or Patau Syndrome can be mostly caused by autosomal non disjunction or robertsonian translocation?
autosomal non disjunction
Organs affected in trisomy 13 or Patau syndrome?
virtually all organs
characteristic findings on those with Patau syndrome?
holoprosencephaly (no division of brain into hemispheres) microcephaly hypotelorism single nostril or proboscis VSD cephalocele microphthalmia omphalocele Cystic renal aplasia polydactyl rocker bottom feet areas of skin aplasia
1 week survival rate Patau Syndrome
3%
1 week survival rate of 40%
Trisomy 13 also poses risk to the mother. True or false?
True
Other aneuploids dont
What risk does trisomy 13 pose to the mother?
Preeclampsia and hyperplacentosis
What does the chromosome 13 carry which predisposes the mother to preeclampsia when bearing pregnancy with Trisomy 13 (patau syndrome)
gene for SFLT-1
Most common trisomy found in 1st trimester loss
trisomy 16
polyploid is rare in later gestations. T or F
True
Counseling, prenatal diagnosis and delivery options for polyploidy is similar to what trisomies?
Trisomy 13 and 18
recurrence risk for triploidy?
1-1.5%
Diandric triploidy in which the extra chromosome comes paternally is also called?
Type 1 triploidy
This results from fertilization of 1 egg by two sperms or single diploid sperm?
Diandric triploidy or type 1 triploidy
Diandric triploidy results in partial or complete molar pregnancy?
Partial
What molar pregnancy occurs mostly during the first trimester? partial or complete
partial molar pregnancy diandric triploidy
Dygynic triploid pregnancy or type 2 triploidy has extra paternal or maternal chromosomal sets?
Maternal
This triploidy occurs when the egg fails to undergo the first or second meiotic division before fertilization?
Dygynic triploidy or type 2 triploidy
a fetus with triploidy expresses asymmetrical growth restriction, what type of triploidy is present?
Type 2
Type of triploidy occuring mostly during the second and third trimester?
Dygynic triploidy
Post zygotic failure to complete an early cleavage division can result in what kind of polyplopidy?
Tetraploidy (92, XXYY or XXXX)
only monosomy compatible with life?
Turner syndrome (45, XO)
most common aneuploidy in first trimester loss?
Turner syndrome (20%)
Turner syndrome is associated with maternal age. T or F?
False
how many percent of pregnancies with turner syndrome yield liveborn nenonate?
1%
A patient grows to have a webbed neck due to cystic hygromas, short stature and impaired cognitive development, what is the most probable genetic abnormality?
Turner Syndrome
What is administered to patients with Turner syndrome to ameliorate for the short stature?
Growth hormone
what is the appropriate prenatal screening test for Turner syndrome?
Cell free DNA test
What form of turner syndrome will need prophylactic gonadectomy for those with y chromosome and streak ovaries?
mosaicism
The extra X chromosome in triple X syndrome is derived from maternal or paternal chromosome?
Maternal
children with triple x syndrome are first diagnosed when due to learning disability and attention deficit disorder and low overall cognitive scores?
School age
For each extra x chromosome in triple X syndrome what happens to the IQ score?
IQ score becomes lower
this is the most common sex chromosome abnormality?
Klinefelter syndrome (47, XXY)
In Klinefelter syndrome, there is no normal virilization. This results in?
gonadal dysgenesis
Due to gonadal dysgenesis, what supplement is needed for those with Klinefelter syndrome?
Growth hormone and estrogen is for Turner syndrome as _____ is to Klinefelter syndrome?
Testosterone
A tall male patient suddenly develops gynecomastia and upon physical exam, presents with testicular atrophy, female pubic hair. What is the possible genetic abnormality?
Klinefelter Syndrome
In 47, XXX or XYY, the more Y chromosomes are present, the more the patients are at risk of?
Congenital abnormalities, medical problems and intellectual disability
Deletions and duplications mostly occur during?
Meiosis
What test permits the identification of deletions and duplications?
Chromosomal microarray analysis
Genetic abnormality presenting as happy puppet appearance with mental retardation, ataxia, hypotonia and seizures. This is due to defect in maternal genes at 15q 11.2-q13
Angelman Syndrome
Genetic abnormality that presents as abnormal laryngeal development which makes a cat like cry together with hypotonia and mental retardation. This is due to defects in 5p 15.2-15.3
Cri-du-chat
Genetic abnormality presenting as hypogonadotropic hypogonadism and anosmia. Genetic defects at Xp22.3
Kallman Syndrome
What genetic abnormality is characterized by obesity, hypotonia, mental retardation, hypogonadotropic hypogonadism and small hands and feet. The genetic defect is at 15q. 11.2-q13 within the paternal genes.
Prader willi syndrome
What genetic abnormality is characterized by cardiac defects, cleft palate, velopharyngeal incompetence, thymic and parathyroid abnormalities and developmental delay. The affected genes are at 22q 11.2
Di George syndrome
Form of translocation that begins when breaks occur in two different chromosomes and broken fragments between them exchange so that each affected chromosome contains a fragment of the other and no chromosomal material is gained or lost in the process.
Balanced or Reciprocal Translocation
What is the risk of major structural or developmental abnormality in apparent balance translocation?
6%
Robertsonian translocations involve only acrocentric chormosomes. What are the acrocentric chromosomes?
13, 14, 15, 21, 22
In Robertsonian Translocation, which arms are retained and fuse at one centromere? p or q arms?
q arms
A child or fetus is found to have a translocation trisomy, what test should be conducted for the parents?
karyotyping and preconceptual counselling
The most common isochromosome involves what part of the gene?
Long arm of the X chromosome (iXq)
This is the etiology of 15% of Turner Syndrome cases?
IXq isochromosome
These abnormal chromosomes are composed of either 2 q arms or 2 p arms of one chromosome fused together. These are also thought to arise when the centromere breaks transversely instead of longitudinally during meiosis II or mitosis
isochromosome
Results from breaks in both the p and q arms of a chromosome, such that the inverted material includes the centromere.
Pericentric Inversion
Abnormal gametes and and abnormal offspring
Results from breaks of both p and q arms of a chromosome but the inverted material does not include the centromere.
Paracentric inversion
Normal gametes and low risk for abnormal offspring
Happens when there is deletion at each end of the same chromosome.
Ring Chromosome
If telomeres are lost, the gene becomes unbalanced. True or false?
False
Even when telomeres are lost, all necessary genetic material are retained and therefore, the gene is still balanced.
A ring X chromosome results in what genetic abnormality?
Turner Syndrome
This happens when an individual has two ore more cytogenetically distinct cell lines that are derived from a single zygote.
Mosaicism
When considering inheritance. What is either dominant or recessive? Phenotype or genotype?
Phenotype
This explains how different mechanisms can result in the asme phenotype
Genetic heterogeneity
indicates that a specific phenotype can be caused by mutations in the different genetic loci
Locus Heterogeity
Describes how different mutations of the same gene may affect presentation of a particular disease
Allelic heterogeneity
explains how different disease state can arise from different mutations in the same gene
Phenotypic heterogeneity
If only one copy of the gene pair determines the phenotype, the gene is said to be dominant or recessive?
Dominant
What are the factors that affect phenotype of an autosomal dominant condition?
Penetrance, expressivity and presence of co dominant genes
This characteristic describes whether or not the dominant gene is expressed at all.
Penetrance
This characteristic determines the degree if manifestation fo the condition that may range from mild to severe
Expressivity
Diseases that only develop when both gene copies are abnormal
Autosomal recessive
this is known to be an inborn deficiency of phenylalanine hydroxylase.
Phenylketonuria
Patients will have hair, eye and skin (albinism) hypopigmentations
What is the treatment for phenylketonuria?
Phenylalanine restriction alone.
Where does the X chromosome of a male person come from? Maternal or paternal?
Maternal
That is why males with X linked diseases cannot have affected sons and most X linked diseases are obtained by males.
X linked dominant diseases mainly affect males or females?
Females because X linked dominant diseases are usually fatal to males
How many percent of their daughters will males with X linked dominant disorders have the disease?
100%
All of them will have the X gene from their father which will be phenotypically expressed
Are all sons affected by the X linked dominant gene?
No
their X chromosome will come from their mother. They will only be affected if their mother also has the X linked disease
Deletions of genes on the long arm of the Y chromosome results in?
Severe spermatogenic defects
Homoplasmy and heteroplasmy of the mitochondria can be determined among offsprings? True or false
False
This is a phenomenon in which the disease symptoms deem to be more severe and to appear at an earlier age in each successive generation
Anticipation
Fragile X syndrome, an X linked disease is dependent on what to determine the degree of clinical normalcy or impairment?
CGG repeats
This is the most common cause of autism or autism like behavior?
Fragile X syndrome
How many repeats of CGG is necessary to affect those with Fragile X syndrome?
45
Unaffected - less than 45
Intermediate - 45-54
premutation - 55-200
full mutation - more than 200
What test are done at prenatal diagnosis for those with history or risk of fragile X syndrome?
Amniocentesis or chorionic villus sampling
An individual presents with unexplained intellectual disability, developmental delay and autism. What possible X linked disorder does the person have?
Fragile X syndrome
This term describes some genes that are inherited but not expressed.
Imprinting
Examples of disease that may form due to imprinting?
Prader Willi syndrome and Angelman Syndrome
This disease is characterized by obesity
and hyperphagia; short stature; small hands, feet,
and external genitalia; and mild mental
retardation and may be caused by maternal gene imprinting with paternal gene inactivation
Prader Willi Syndrome (microdeletions and disruptions at 15q11.3-q13 of the paternal gene)
This disease is characterized by severe intellectual
disability; normal stature and weight; absent
speech; seizure disorder, ataxia and jerky arm
movements; and paroxysms of inappropriate
laughter. This may be caused by paternal gene imprinting with maternal gene inactivation.
Angelman Syndrome (microdeletions and disruption at 15q11.2-q13 of the maternal gene)
According to ACOG, all pregnant women should have the option of what test for genes?
Aneuploidy screening and prenatal genetic diagnosis
What test is commonly done to test for chromosomal abnormalities?
Karyotyping or cytogenic analysis
During karyotyping, the cells are arrested at metaphase, what technique is most commonly done which yields the G-bands?
Giemsa staining
This technique can be used for rapid identification of
a specific chromosome abnormality and for
verification of suspected microdeletion or duplication
syndromes, such as the 22q11.2 microdeletion. (Di George syndrome)
Fluorescence In Situ hybridization (FISH)
Done when diagnosis affects management of pregnancy. Used for rapidness of about 2 days.
This test is 100 times more sensitive than standard
karyotyping and detects microduplications nad
microdeletions as small as 50 to 100 kilobases.
chromosomal microarray analysis
This genetic test is offered as a
first-tier test when fetal structural abnormalities are
identified.
CMA
In pregnancies at increased risk for autosomal
trisomy based on aneuploidy screening, what is the recommended test?
Karyotyping of FISH plus Karyotyping
If CMA fails to arrive at a diagnosis, what other test may be done?
Whole Genome Sequencing and Whole Exome sequencing
Genome - for genome
Exome - only the DNA coding regions
What DNA fragments come from apoptotic trophoblasts which are used in testing for single gene disorder, Trisomy testing, fetal sex determination and RHD genotype?
Cell Free DNA
