Genetics Flashcards
What does cytogenetics refers to?
The study of chromosomes, their structure, and their inheritance mechanism.
How do we analyze chromosomes?
Chromosomes analysis involves examination of chromosomes of a dividing cell by Light Microscopy.
What is the Colcemid treatment? What phase of mitosis do they affect?
Lymphocytes reach their peak rate of mitosis after approximately 72 hours. The dividing cells are arrested in metaphase with chemicals that inhibit the mitotic spindle. (Colcemid is a derivative of colchine).
What is triploidy?
There are 3 chromosomes instead of a pair making the total count 69.
Male with trisomy results in ?
Down syndrome 47, XY +21
How does FISH tecnique works?
FISH tecnique, as all other hybridization techniques, reliew on the complementarity of the DNA molecule.
What can we find with a SNP array?
We will find single nucleotide polymorphisms.
What are the general indications for requesting a DNA array analysis?
- Multiple malformations or unknown dysmorphism syndrome.
- Unexplained fetal demis, especially if history of more than one fetal demise or stillbirth.
- Psychomotor developmental delays, especially in the context of short stature, dysmorphims, and or multiple malformations
- Growth disturbances in girls, quite often, these are caused by Turner Syndrome/Monosomy X.
- Increased risk for a fetal chromosomal distrubance during pregnancy.
- Positive family history for chromosomal abnormality; a copy of the abnormal chromosomal report should be review.
What are the general indications for requesting a G-banded chromosome Analysis
- Recurring uncexplained miscarriages or stillbirths. If two or more unexplained miscarriages occur, teh parents should undergo a G-banded chromosome analysis, which will detect balanced arragements.
- Infertility, especially when planning invasive fertilization techniques such a s intracytoplasmic sper injection (ICSI), to exclude a balanced translocation orsex chromosome abnormality.
- First-line testing when Down syndrome, Turner syndrom, Klinfefelter syndrome, or autosomal trisomy is suspected. A G-banded analysiss will detect robertsonian translocations, whereas a DNA array analysis would only dectec increased dosage. G-banded analysis will also dectect low-level of mosaicism.
- Characterization of malignant tumors. Almost all neoplasisa manifest chromosomal aberrations. A chromosomal analysis of tumor tissue can be of diagnostic, prognostic, and/or therapeutic value.
Where is the genomic DNA usually extracted from?
The genomic DNA is extracted from nucleated cells of blood (lymphocytes).
What is necessary for RNA analysis?
In contrast to DNA alalysis, RNA testing requires cells in which the repective gene is expressed. An organ biopsy may be nexessary (e.g. liver biopsy), and teh cells need to be processed rapidly, since RNA is unstable.
How do we select the best method for testing?
Point mutuations and very small deletions are easily accessible for PCR-based methods such as direct sequencing, but larger deletions, duplications, or triplet repeat expansions require special methods for genomis quantification or Southern blot analysis. On the other hand, imprinting mutations in which the genomic imprinting is defective need to be identified with special methylation tests.
What is Linkage analysis based of?
What is the LOD score
Linkage analysis is based on the fact that disease-causing mutations are inherited jointly (linked) with the genetic markers located in their immediate vicinity on the same chromosomal strand.
Since a linkage between gene and marker can be lost through recombination and since linkage can be a spurious chance effect (specially in small families), such an analysis can only result in probabilities. Such probabilities are represented by way of logarithm or the logarithm of the odds score (LOD) The higher the LOD score, the larger the probability that a disease-causing gene is present in this region.
what is Angeogenic Potential??
It is the capicity for tumor cells to form new blood vessels and capillaries
What is Burkitt Lymphoma
A general name for several types of B-cell malignancies, result s from a translocation between chromosomes 8 and 14. The translocation of genetic materaial moves the proto-oncogene transcription factor.
What kind of disease is this? Dominant? recessive ? X-linked? Gene?
Symptoms: Bilateral, massive enlargement of kidneys due to multiple large cysts. 85% of cases are due to mutations.
Autosomal dominant polycystic kidney disease (ADPKD)
Mutation in PKD1 (chromosome 16; 16 letters in “polycystic kidney”); remainder due to mutation in PKD2 (chromosome 4).
Familial Hypercholesterolemia
Elevated LDL due to defective or absent LDL receptor. Leaads to severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas. (classically in the achilles tendon).
Autosomal Dominant
Duchenne Muscular Dystrophy
X-linked Recessive
Disorder typically due to frameshift (deletions, duplications, or nonsense) mutations, truncates dystrophin protein, inhibited muscle regeneration. Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscles due to fibro fatty replacement of muscle. Gowe maneuver- patients use upper extremities to help them stand up. Waddling gait. Onset before 5 years of age. Dilated cardiomyopathy is common cause of death. Western blot confirm diagnosi.
Becker Muscular Dystrophy
X-linked recessive
Disorder typically due to non-frameshift insertions in dystrophin gene (partially functional instead of truncated). Less sever than Duchenne. Onset in adolescense or early adulthood. Deletions in this gene can cause both Becker and Duchenne.
Hereditary Spherocytosis
Autosomal Dominant
Spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia; increase MCHC (mean cell hemoglobin concentration), and increase RDW (red blood cell distribution width). Treatment: splenectomy.
In hereditary spherocytosis, red blood cells have an abnormal shape and are more fragile than normal red blood cells. These abnormal cells are broken down when they pass through the spleen, an organ near the ribcage that cleans dead cells and germs from the blood.
The breakdown of these cells can cause anemia (a low level of red blood cells
Huntingotn disease
Autosomal Dominant
Findings: depression, progressive dementia, choreiform movements, and caudate atrophy. High dopamine, low GABA, low ACh in the brain. Gene on chromosome 4; trinucleotide repeat disorder (CAG). Demonstrates Anticipation: increase repeats in future generations and lower age of onset. “Hunting 4 food”.
Fragile X Syndrome
X-linked recessive
Defect affecting teh methylation and expression of the FMRI gene. the 2nd most common cause of genetic intellectual disability (After Down Syndrome). Findings: post-pubertal macroorchidism (enlarge testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse. Trinucleotide disorder (CGG)
What disease is display in the karaotype?
Cri-du-chat syndrome = Cry of the cat
Congenital microdeletion of short arm of chromosome 5 (46 XX or XY, 5p-) Findings: microcephaly, moderate to sever intellectual disability , high pitched crying/mewing, epicanthal folds, cardiac abnormalities.
What disease is depicted in the image? Deleted region is long arm of chromosome 7.
Williams Syndrome
Congenital microdeletion of long arm of chromosome 7. Deleted region includes elastin gene.. Findings: distinctive “elfin” facies, intellectual disability, hypercalcemia (increase sensitvitity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.
What’s wrong with this person? What’s the disease name? (Trisomy 13)
Patau Syndrome
Findings: severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, (Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy.) Polydactyly (extra fingers on the hands or toes on the feet. Since the extra fingers or toes are present at birth, they are called a congenital anomaly.) Congenital heart disease, cutis aplasia. Death usually occurs within 1 year of birth. Firt trimester screen show low free beta-hCG (It is made by cells that form the placenta, which nourishes the egg after it has been fertilized and becomes attached to the uterine wall.) low PAPP-A (pregnancy-associated plasma protein A) and high nuchal translucency.
What disease happens from a FBN1 gene mutataion on chromosome 15? This disease is autosomal dominant?
Marfan Syndrome
Defective fibrin (scaffold for elastin), connectivie tissue disorder affecting skeleton, heart, and eyes. Findings: tall with long extremities, pectus excavatum, hypermobile joints, and long, tapering fingers and toes (arachnodactyly, is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand).
Cystic medial necrosis of aorta, aortic incompetence and dissecting aortic aneurysms; floppy mitral valve. Subluxation of lenses, typically upward and temporally.
What disease is caused from a mutation on chromosome 22? and (22q11) Are they AR? AD?
Mutation on chromosome 22 is autosomal dominant Neurofibromatosis type 2. Findings: bilateral acoustic shwannomas, juvenile cataracts, meningiomas, and epedymomas. “Type 2=22”.
(DiGeorge Syndrome is 22q11: deletion involved in long arms of chromosome 22. Result in facial, cardiac, and immunological abnormalities. Thymic aplasia, and failure of parathyroid formation. pts present with infections and cleft palate).
(MEN) Multiple Endocrine Neoplasias
Autosomal Dominant
Several distinct syndromes (1, 2A, 2B) characterized by familial tumors of endocrine glands, inclucding those of the pancreas, parathyroid, pituitary, thyroid, and adrenal medulla. MEN 1 is associated with MEN1 gene, MEN 2A, and 2B are associated with RET gene.
What disease is caused by a mutation chromosome 17? is it AR/AD?
Neurofibromatosis type 1 (von Recklinghausen disease)
Neurocutaneous disorder characterized by cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, lisch nodules (pigmented iris hamartomas). Autosomal dominant, 100% penetrance, variable expression. Caused by a mutation on the NF1 gene on chromosome 17.
What disease is Approxi. 70% of the Patients ; Causes severe demyelination, thereby impairing nerve conduction velocity? AR? AD?
Charcot-Maire-Type 1
Autosomal Dominant 17p, PMP22 protein
what disease is typical of Dwarfism; Short limbs, larger hed, trunk size is normal?
Achondroplasia: Fibroblast growth factor, autosomal dominant.
