Cytogenetics and Testing Flashcards
Test that focuses on the centromere of the chromosome
C- banding
What is mosaicism?
Two or mor chromosome complements in the same person (i.e both a normal chromosome count and an abnormal chromosome count)
Patient presents with short stature, edema at birth,broad chest, webbed neck, increased weight and obesity. What is the most likely diagnosis? What is karyotype? What is the likelihood of survival? What is the cause? What other symptoms may be present?
Turner syndrome- 45, X
1% chance of survival.
Usually due to paternal non-disjunction
Additional symptoms: Low hariline, low-set ears, gonadal dysgenesis, small fingernails, deficiency in spatial perception, widely spaced nipples
P arm is basically non existence
Acrocentric
Test used to identify Dark regions vs. Lighter regions? What region do the darker regions represents? The lighter regions?
G- Banding Giemsa, Q-banding
Darker- heterochromatin (AT rich)
Lighter- Euchromatin (CG RICH)
Variation in # of chromosome sets.
What are the different types?
Polyploidy
Triploid- 3 x the haploid # (69)
Tetraploid- 4 x the haploid # (92)
Will efforts that are in place to reduce the birth of children with Tay Sachs disease affect the carrier frequency as well??
No. Carrier frequency will still be the same but if those carriers don’t mate then the affected frequency will decrease.
Patient presents with cleft lip/ palate, flexed fingers with polydactyly, bulbous nose, low-set malformed ears, holoprosencephaly. What is the most likely diagnosis? What is karyotype? What is the likelihood of survival? What other symptoms may be present?
Patau Syndrome- 47, XY, +13
Lethal in the 1st year of life
Additional symptoms: Hypoplastic ribs, scalp defects, visceral and genital anamolies, cerebral malformation, small abnoraml skull, ocular hypotelorism
*Patau Syndrome has 13 letters!
Which groups are acrocentric? All other groups are___________.
D and G
Metacentric
Which type of triploidy aborts earlier?
Digyny
How are chromosomes arranged? How are they grouped?
Largest to smallest
According to the position of the centromere
Should screening be done based on ethnicity?
No! Because there’s a lot of admixture and genes don’t know color
Foresight is what type of screening technique?
Expanded carrier screening
What event leads to production of a patiral hydatidiform mole?
Fertilization of an ovum by two sperm leading to an abnormal placenta
What is the cause of edema seen in Turner’s syndrome?
A blockage in the lymphatic system
A mutation in MSH16 is associated with what type of cancer?
Colon cancer
*Can also be associated with breast cancer
Causes of a complete mole
More commonly due to doubling of haploid sperm at fertilization of anucleate egg
Complete paternal UPD
Rarely, two haploid sperm fertilizing an anucleate ovum
Enlargement of the trophoblast ( forms the placenta)
Overgrown placenta with little to no non-placental elements
If recurring, may be due to lack of maternal imprinting of otherwise normal conceptus – autosomal recessive trait
__________% of babies with down syndrome are born to mothers under 35.
80
What event leads to a tetraplod cell?
Occurs when you have a diploid egg and two sperm fertilize it
VERY RARE
Patient presents with failure to thrive at birth, hypotonia, develop veracious appetite in early childhood, and obesity. What is the most likely diagnosis? What is karyotype? What is the cause? Additional symptoms?
Prader-Willi syndrome- 46, XY, del (15) (q11-q13)
Paternal deletion of long arm of 15th chromosome
Small hands and feet, hpogonadism, mental disability
Vertical patter on inheritance
Number of males= number of females
Male to male transmission
Every affected child has an affected parent
Autosomal dominant
Burkitt Lymphoma
B- cell tumor of the jaw
Due to translocation of chromosomes 8 and 14 at q24 and q32
Results in increased unregulated expression of MYC
* Note: the immunoglobulin heavy-chain is located on 14q32, so you can imagine that there will be problems with B cells
Role of Ideograms
mapping system that allows them to refer to specific portions of particular chromosomes with extreme accuracy
Patient presents with g, cat like crying, low birth weight, microencephaly, hypertelorism, epicanthal folds, and micrognathia. What is the most likely diagnosis? What is karyotype? What is the cause? What are additional symptoms?
Cri du chat syndrome- 46, XY, del(5)(p14.2)
Cause: Delection of short arm of chromosome 5
Additional symptoms: low set ears
What is the concept of rescuing during UPD?
Cell realizes that it has too many chromosomes and tries to “kick one out”. The cell has to be sure to kick out the right chromosome though, to insure that there is one maternal chromosome and one paternal chromosome.
What are the causes and characteristics of deletion or duplication?
Deletions or duplications may be terminal or intersitial.
Causes:
- Breakage and loss of centromere segment
- Unequal crossing over between misaligned homologous chromatids
- Abnormal segregation of translocation
Vertical pattern
Number of males= number of females
All affected females’ children are affected (none of affected males’ children are affected
Mitochondrial
What test are used for prenatal diagnosis?
Amniocentesis- the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus.
Chrorionic villus sampling- another way to test the placenta
Horizontal pattern of inheritance
Number of males= number of females
Consanguinity increases risk
Autosomal recessive
Patient presents with partial hydatidoform mole. What is the most likely disorder? What is the most likely cause of the disorder? What are the visible attributes of the partial hydatidorm mole?
Diandry (69, XXX or 69, XXY or 69, XYY)
1 egg is fertilized by two sperm possibly due to genterically determined weakness of the zona pellucida that allows to sperm to fertilize.
Partial hydatidiform mole presents with a large placenta with degenerate chorionic villi that form fluid-filled sacs
Nondisjunction at which stage of meiosis is worse? Why?
Meiosis I. If nondisjunction occurs at Meiosis I, you will produce cells that are only trisomy or monosomy because it prevents separation of homologous chromosomes. Nondisjunction at Meiosis II will produce two diploid cells, 1 monosomy, and 1 trisomy. Fetus has a greater chance of being normal
Vertical pattern
All daughters of affected males are affected, but none of the sons
Number of females> number of males
No male to male transmision
Often fatal in males
X- linked dominant
Patient presents with hypotonia, flat face, slanted palpebral fissures, epicanthic folds. What is the most likely diagnosis? What is karyotype? What is the likelihood of survival? What is the cause? What other symptoms may be present?
Down syndrome- 47,XX, +21
Nondisjunction during Meiosis I
1/600 births
Additional symptoms:
- Pelvic dysplasia, cardiac malformations
- Short, broad hands, transverse crease, hypoplasia
of 5th finger, intestinal atresia, high arched/cleft palate
*Legal age to Drink is 21!
Different triploidy karyotypes. Which is most common?
69,XXX
69, XXY
69, XYY (most common)
In what disorder is the carrier frequency for AA males 1/10?
G6PD
A ring chromosome can be a cause of what syndrome? What is the cause of ring chromosomes
Turner syndrome
Defect in telomeres
For which population (s) are hemoglbinopathy (SC, SS, beta thalassemia) screened for?
African American
West african
Hispanic
Italian
Which part of the Barr Body still remains active and still codes for proteins?
Pseudoautosomal region (PAR)
Only males affected, related though carrier females
No male to male transmission
Lyonization leading to affected females
Apparent male to male transmission
X-Linked Recessive
In a pedigree, the first affected individual in the family who brought the family to medical attention is the ________.
Proband
The WAS gene can cause spectrum of hematopoietic disorders like:
Wiscott-Aldrich Syndrome
Eczema
Microthrombocytopenia
Severe and recurrent infections
P arm slightly shorter than q arm
Submetocentric
Trisomy X is the result of________. In Trisomy X about ______ of patients have some learning problems.
Maternal nondisjunction meiosis I; 70%
Importance of XIST gene?
Expressed in inactivation X chromosomes.
*lack of this gene can be indicative of Turner’s syndrome
Patient presents with head-body dispropotion with head relatively large and small, an abnormal placenta, and syndactyly of third and fourth fingers. What is they likely problem? What are the possible karotypes? What is cause?
Digyny- 69, XXX or 69, XXY
Due to nondisjuntion of an entire chromosomes set at meiosis I or Meiosis II that causes a binucleate, diploid oocyte.
Which chromosomes are acrocentric?
13,14,15, 21, 22
You want to detect microscopic deletions and visualize obvious chromosome anomalies. Which test should you use? How does it work? What are the limitiations?
Fluorescence in-situ hybridization
Nucleic acid probes are hybridized to unique chromosomal DNA sequences. Probes are labed with fluorescent dye, which is visible under a specific wavelength. Can be used in metaphase and anaphase.
Limitations: Does not provide information on point mutations or other small genetic aberrations
What is an example of a gene outside of PAR that does not have a similar copy on the Y chromosome and is therefore expressed in higher levels in females?
Steriod sulfatase
*think calice cat*
In ideograms, orientation is based on the ________. Where are lower numbers located?
Centromere; Proximal to the centromere
Primary role of staining chromosomes
To study peripheral blood lymphocytes and chromosomes during mitosis
What is a Robersionian translocation?
Translocation between two acrocentric chromosomes
Which usually more harmful deletions or duplications?
Deletions
You want to be able to detect very small deletions or duplications. Which test should you use? How does it work?
Coparative genomic hybridization
Flourophore-tagged DNA from the patient is applied to the microarray.
Patient presents with a tall, thin stature, hypogonadism, gynecomastia, infertility due to failed germ cell development. What is the most likely diagnosis? What is karyotype? What is the likelihood of survival? What is the cause? What other symptoms may be present?
Klinefelter syndrome- 47, XXY
Chances of survival are very high
Due to in part to paternal meiosis I and also in part to maternal meiosis I
Additional symptoms: Variable learning problems, poor psychosocial development
*48, XXYY; 48, XXXY; 49, XXXXY tend to be more severe
Symbolism for Robertsonian Translocation
der,t, rob
Derivative translocation of acrocentric chromosomes
You want to look at genetic material of the fetus through the maternal serum. You also want to be able to determe which chromosomes those DNA fragments came from. Which test should you use? What are the benefits of this test? How is chromosomal origin identified?
Cell free DNA anaylsis
Non-invasive
Detection rates close to 99%
Chromosomal origins are identified through massive parallel shotgun sequencing
Which type of aneuploidy abnormality has the highest frenquency of miscarriages? Which has the lowest?
45, X
XXX, XXY, XYY (often not discovered until person tries to procreate)
Patient presents with attention deficits, hyperactivity, impulsiveness. Patient is tall. What is the most likely diagnosis? What is karyotype? What is the likelihood of survival? What is the cause? What other symptoms may be present?
47, XYY
High chance of survival
Due to paternal nondisjunction meiosis II
Additional symptoms: Normal fertility, normal intelligence but speech and other therapies may be needed
In which type of inversion is the risk for carrying an abnormal viable offspring higher? Why?
Pericentric; If you have a pericentric inversion those chromosomes cannot line up in metaphase becuase the centromere has changed its location and the genes are on opposite side!
Dats Brazy!
Histone Octamer components
Two copies of H2A, H2B, H3, and H4
For which population (s) is Tay-Sachs Disease screened for?
Ashkenazi Jewish
French Canadian
Phildelphia chromosome
Due to translocation of chromosomes 9 and 22 at q34 and q11.
Leads to longer ABL (tyrosine kinase) protein with enchanced activity and actiation of oncogene BCR
What is the chance of a healthy sibling of an affected person with an AR condition to be a carrier?
2/3
What two events can occur to lead to a triploid cell? Which is more common?
- 1 egg is fertalized by 2 sperm (most common)
- A haploid egg is fertilized by one diploid sperm (less common)
*Very selective process so usually diploid sperm aren’t able to fertilize an egg
If you want to look at large chromosome delections and duplications and chromosome structure. What test should you use?
Karyotype
Which information should be collected in the family history for a pedigree?
Three generations
Half versus full siblings
Age, birthdate, or year of birth
Relevant health information
Diagnosis, age at diagnosis
Age at death or years of birth/death
Cause of death
Ethnic background for each biological grandparent
In pedigree, person seeking genetic services is the _________
Consultand
Patient presents with low body weight, closed fists, rocker-bottom feet, hypertonia, microcephaly and cardiac and renal malformations. What is the likely diagnosis? What is karyotype? What is the likelihood of survival? What are additional symptoms?
Edwards Syndrome- 47, XY, +18
95% of cases are lethal in the 1st yr
Additional symptoms: Narrow hips with limited abduction, short sternum, prominent occiput, micrognathis, fine/ small facial features, mental retardation
*The legal age to Elect someone is 18!
Patient presents with short stature, severe mental disability, spascitty, seizures, and uncontrollable laughter. What is the most likely diagnosis? What is karyotype? What is the cause?
Angelman Syndrome- 46, XX, del (15)(q11-q13)
Maternal deletion of long arm of 15th chromosome
“maternal imprinting”
Example of a disorder that results from isochromosomes.
Pallister Killian syndrome- 47, XY,i (12p)
Symptoms: extremely weak muscle tone in infancy and early childhood, intellectual disability, distinctive facial features and sparse hair, areas of unusual skin pigmentation
*You’ve killed a whole arm of genetics.
What is the chance of conceiving a child with down syndrome at age 35?
1/238
What’s the difference between a screening and diagnostic?
Screening- Identifies those at risk for a particular outcome
Diagnostics- Provide confirmed result that an individual has a medical condition of interest or genetic anomaly
What are the limitations of Whole Genome/ exome sequencing?
Insuffiecient capture of some exons
No triplet repeat, large deletions or duplications, translocations, or inversions are detected
In the second trimester of pregancy what proteins can be screened for to determine down syndrome of the fetus? What would the tests show for other types of aneuploidy?
hCG (high), Unconjugated estriol (low), Inhibin A (high), and dimeric protein A (Low)
Trisomy 18 (Edwards)
hCG (very low), Unconjugated estriol (low), Inhibin A (unchanged), and dimeric protein A (unchanged)
Trisomy 13 (Patau)
hCG (normal), Unconjugated estriol (normal), Inhibin A (normal), and dimeric protein A (increased)
Turner (45X)
hCG (very high), Unconjugated estriol (decreased), Inhibin A (very high), and dimeric protein A (decreased)
Importance of telomeres
What happens when they are missing/malfunctioned?
Maintain chromosome stability
Keep ends from being degraded by nucleases
When missing, there is a pause in cell cycle to allow error to be corrected or may indicate pathway to apoptosis
Types of genetic screenings
Carrier screening (commonly used for prenatal or preconception testing)
Prenatal screening (for 1st and 2nd trimester screening, sequential screening, and cell free DNA screening)
Screening to determine complex disease risk (for multifactorial conditions)
Patient presents with progressive neurological disorder, loss of sensation and wasting of muscles in the feet, legs, and hands, due to damaged peripheral nerves. What is the most likely diagnosis? What is karyotype? What is the cause?
Charcot- Marie-Tooth- 46, XY, dup(17)(p12)
Duplication of chromosome 17
* Think we have 29 teeth, 17 at the top and 12 at the bottom
What is UPD? Why is this a problem?
Cell has either chromosomes that are both from the mother or both from the father. Mother and father both pass on important genes, some genes are only expressed on paternal chromosome and some genes are only expressed on maternal chromosome (imprinting).
You are not concerned with the entire chromosome but you want to study single, specific gene. What test should you use? What diseases can detected for which this test? What are the limitations?
Single gene/ specific mutation testing
Can detect for CF, SCD, and DMD
Limitations: You may test the wrong gene based off of certain symptoms, which could allow for a misdiagnosis.
When are prenatal testing procedures used?
For the couple who is a 1 in 4 or higher risk
Type of inversion that includes centromere
Pericentric
Patient presents with congenital heart disease, characteristic facial features, learning difficulties, and immune deficiency. What is the most likely diagnosis? What is karyotype? What is the cause?
Velocardiofacial syndrome/ DiGeorge Syndrome
Karyotype: 46, XX, del(22)(q11.21-q11.23)
Due to deletion of 22q11
You want test a phenotype associated with multiple genes at the same time. What test should you use? What diseases can be tested using this test?
Multi-gene panel testing
Deafness, mental disability, seizures, ataxia, and autism
For which population (s) is Maple Syrup Urine Disease screened for?
Mennonite/ Amish
P and q arms roughly the same size
Metocentric
For which population (s) is cystic fibrosis screened for?
Caucasian
