Block 1 Exam 4 Part 1 Flashcards
Which types of inheritance, males and females, are equally likely to transmit the trait to their offspring, and it shows a vertical transmission?
Autosomal Dominant
Which of the factors that affect expression of disease-causing genes refers to genes that exert affects on multiple aspects of physiology or anatomy?
Pleiotropy
The study of chromosomes and their abnormalities is called ___.
cytogenetics
What techniques are used to arrest dividing somatic cells in metaphase, when chromosomes are easiest to see?
Spindle poisons like colchicine and colcemid.
What solution causes swelling of cells and better separation of individual chromosomes?
Hypotonic (low-salt) solution.
What process makes chromosomes easier to identify by producing light and dark bands?
Staining materials that are absorbed differently by different parts of chromosomes.
In which phase are chromosomes maximally condensed and easiest to observe?
Metaphase
How long are peripheral lymphocytes usually cultured before chromosome analysis?
48 to 72 hours.
What substance is added to produce metaphase arrest during chromosome analysis?
Colcemid
What is used to rupture the cell nucleus during chromosome analysis?
Hypotonic saline solution.
What is the process called where chromosomes are photographed and arranged according to length?
Karyogram (or karyotype).
What does the term “karyotype” refer to?
The number and type of chromosomes present in an individual.
What technology is currently used to display chromosomes?
Computerized image analyzers.
What term describes a chromosome with its centromere near the middle?
Metacentric
What is a chromosome called when its centromere is near the tip?
Acrocentric
What term is used for chromosomes with centromeres located between the middle and the tip?
Submetacentric
What is the name of the tip of each chromosome?
Telomere
What label is given to the short arm of a chromosome?
p
What label is given to the long arm of a chromosome?
q
In metacentric chromosomes, how are the p and q arms designated?
By convention, where the arms are of roughly equal length.
How is a normal female karyotype designated?
46,XX
How is a normal male karyotype designated?
46,XY
What development in the 1970s improved the detection of chromosomal abnormalities?
Staining techniques that produce chromosome bands.
How does chromosome banding help in karyotyping?
It helps detect deletions, duplications, and other structural abnormalities, and aids in identifying individual chromosomes.
How are the major bands on each chromosome designated?
They are systematically numbered.
What does “14q32” refer to?
The second band in the third region of the long arm of chromosome 14.
How are subbands designated in chromosome banding?
By decimal points following the band number (e.g., 14q32.3).
What was the first staining method used to produce specific banding patterns?
Quinacrine banding (Q-banding).
Which staining method has largely replaced Q-banding?
Giemsa banding (G-banding).
What is required to produce G-bands?
Giemsa stain after partial digestion of chromosomal proteins by trypsin.
What does reverse banding (R-banding) do?
It reverses the usual white and black pattern seen in G-bands and Q-bands.
Which banding technique is helpful for staining the distal ends of chromosomes?
Reverse banding (R-banding).
What does C-banding specifically stain?
Constitutive heterochromatin near the centromere.
What areas do nucleolar organizing region stains (NOR stains) highlight?
Satellites and stalks of acrocentric chromosomes.
Why are C-banding and NOR staining techniques useful?
They are useful in identifying unknown chromosomal material.
What stages of cell division are chromosomes stained during high-resolution banding?
Prophase or early metaphase (prometaphase).
How does staining chromosomes during prophase or prometaphase affect the number of observable bands?
The number of observable bands increases from about 300 to 450 to as many as 800.
What advantage does high-resolution banding provide compared to conventional banding?
It allows detection of less obvious abnormalities usually not seen with conventional banding.
What does the fluorescence in situ hybridization (FISH) technique use to detect specific DNA sequences?
A labeled single-stranded DNA segment (probe).
What types of chromosomes can be used in FISH?
Denatured metaphase, prophase, or interphase chromosomes.
How is the location of a probe visualized in FISH?
Under a fluorescence microscope.
What does it indicate if a FISH probe hybridizes to only one chromosome in a patient?
The patient likely has a deletion on the chromosome that failed to hybridize.
How does FISH resolution compare to high-resolution banding approaches?
FISH provides considerably better resolution and can detect deletions as small as 1 million base pairs (1 Mb).
What are two common deletion syndromes detected by FISH?
Prader-Willi syndrome (microdeletion of 15q11.2) and Williams syndrome (microdeletion of 7q11.2).
How are extra copies of a chromosome region detected using FISH?
The probe hybridizes in three or more places instead of two.
What can combinations of FISH probes detect?
Chromosome rearrangements such as translocations.
What is an advantage of using FISH with interphase chromosomes compared to traditional methods?
It allows for faster analyses and diagnoses because it is not necessary to stimulate cells to divide to obtain metaphase chromosomes.
What are common applications of FISH analysis of interphase chromosomes?
Prenatal detection of fetal chromosome abnormalities and analysis of chromosome rearrangements in tumor cells.
How has the FISH technique been extended to detect multiple numerical abnormalities?
By using multiple probes, each labeled with a different color, to test several common numerical abnormalities simultaneously.
What does spectral karyotyping involve?
Using varying combinations of five different fluorescent probes and special cameras to uniquely color each chromosome for identification.
What is the advantage of spectral karyotyping?
It is useful for identifying small chromosome rearrangements.
What technique is used to detect losses or duplications of whole chromosomes or specific chromosome regions?
Comparative genomic hybridization (CGH).
How is DNA labeled for CGH analysis?
DNA from the test source is labeled with one color (e.g., red) and DNA from normal control cells is labeled with a second color (e.g., green).
In CGH, what does a red signal indicate on a chromosome?
The region is duplicated in the test DNA.
In CGH, what does a green signal indicate on a chromosome?
The region is deleted in the test DNA.
What type of cells is CGH especially useful for analyzing?
Cancer cells
What is a major limitation of CGH when used with metaphase chromosomes?
It cannot detect deletions or duplications smaller than 5 to 10 Mb microscopically.
What resolution can array CGH (aCGH) provide?
Resolution to 50 to 100 kb or even less.
What does cytogenomic microarray (CMA) utilize to detect smaller genomic variations?
Microarrays with single nucleotide polymorphisms (SNPs) arranged very closely.
What is the resolution capability of cytogenomic microarrays (CMA)?
Detection of deletions and duplications of less than 20 kb.
What additional features does cytogenomic microarray (CMA) offer compared to array CGH?
Detection of loss of heterozygosity and uniparental disomy.
Do array CGH (aCGH) and cytogenomic microarrays (CMA) require dividing cells for analysis?
No, they do not require dividing cells.
How much DNA is needed for analysis using array CGH (aCGH) and cytogenomic microarrays (CMA)?
Less than a microgram of DNA is sufficient for analysis of the entire genome.
What is a primary disadvantage of array CGH (aCGH) and cytogenomic microarrays (CMA)?
They cannot detect balanced rearrangements of chromosomes, such as reciprocal translocations or inversions.
What is the term for a cell that contains a complete set of extra chromosomes?
Polyploidy
What is the karyotype designation for triploidy?
69,XXX (or other combinations of sex chromosomes).
What is the karyotype designation for tetraploidy?
92,XXXX (or other combinations of sex chromosomes).
What is the most common cause of triploidy?
Fertilization of an egg by two sperm cells (dispermy).
What are some effects of having extra chromosomes due to polyploidy?
Multiple anomalies such as defects of the heart and central nervous system.
Why do most triploid conceptions result in spontaneous abortion?
Because of the large amount of surplus gene product leading to severe developmental issues.
What is a rare cause of tetraploidy?
Mitotic failure in the early embryo or fusion of two diploid zygotes.
How long do infants with tetraploidy typically survive?
They usually survive for only a short period.
What term describes cells with a multiple of 23 chromosomes?
Euploid
What is the chromosome count for triploidy?
69 chromosomes
What is the chromosome count for tetraploidy?
92 chromosomes
Are polyploid conditions compatible with long-term survival?
No, all polyploid conditions are incompatible with long-term survival.
What typically happens to most polyploid conceptions?
They are spontaneously aborted.
What term describes cells with missing or additional individual chromosomes?
Aneuploid
What are the two main types of autosomal aneuploidy?
Monosomy (one copy of a chromosome) and trisomy (three copies of a chromosome).
Are autosomal monosomies typically compatible with survival to term?
No, autosomal monosomies are nearly always incompatible with survival to term.
Why do some trisomies produce less-severe consequences than monosomies?
The body can tolerate excess genetic material more readily than it can tolerate a deficit of genetic material.
What is the most common cause of aneuploidy?
Nondisjunction during meiosis.
What can result from nondisjunction during meiosis?
A gamete that either lacks a chromosome or has two copies of it, leading to a monosomic or trisomic zygote, respectively.
In which stages of meiosis can nondisjunction occur?
Meiosis I or Meiosis II.
What is the karyotype for Trisomy 21?
47,XY,+21 or 47,XX,+21.
What is the most common autosomal aneuploid condition compatible with survival to term?
Trisomy 21 (Down syndrome).
What is a highly consistent feature of Down syndrome that aids in diagnosis?
Decreased muscle tone (hypotonia).
Are males with Down syndrome typically fertile?
No, males with Down syndrome are nearly always sterile, with very few reported cases of reproduction.
What percentage of females with Down syndrome fail to ovulate?
Approximately 40%.
What is the risk for a female with Down syndrome to produce a gamete with two copies of chromosome 21?
50%
Why is the risk of producing affected live-born offspring lower than 50% in women with Down syndrome?
Because about 75% of trisomy 21 conceptions are spontaneously aborted.
What can be said about the majority of cases of trisomy 21 in relation to new mutations?
Nearly all cases of trisomy 21 can be regarded as new mutations.
What is tissue-specific mosaicism?
Mosaicism confined to certain tissues, which can complicate diagnosis due to cytogenetic analysis being based on a single tissue type.
How can mosaicism affecting the germline of a parent influence the recurrence of Down syndrome?
It can lead to multiple recurrences of Down syndrome in the offspring.
What is the recurrence risk for Down syndrome among mothers younger than 30 years?
About 1%, which is approximately 10 times higher than the population risk for this age group.
What is the karyotype for Trisomy 18?
47,XY,+18.
What is another name for Trisomy 18?
Edwards syndrome
What is the most common congenital heart defect seen in Trisomy 18?
Ventricular septal defects (VSDs) with dysplasia of multiple heart valves.
What is the karyotype for Trisomy 13?
47,XY,+13
What is another name for Trisomy 13?
Patau syndrome.
What percentage of individuals with Trisomy 13 have heart defects?
80%
What is cutis aplasia, and how can it be useful in diagnosing Trisomy 13?
Cutis aplasia is a defect of the skin on the scalp, particularly on the posterior occiput, and can be a diagnostic clue for Trisomy 13.
What is the karyotype for Turner Syndrome?
45,X
What type of kidney defects are seen in Turner Syndrome, and how do they impact health?
Structural kidney defects are present in about 50% of individuals, but they usually do not cause medical problems.
How does Turner Syndrome affect spatial perceptual ability and intelligence?
There is typically some diminution in spatial perceptual ability, but intelligence is usually normal.
What is the karyotype for Klinefelter Syndrome?
47,XXY.
What reproductive issues are associated with Klinefelter Syndrome?
Most males with Klinefelter Syndrome are sterile due to atrophy of the seminiferous tubules.
What is a common secondary sexual characteristic observed in Klinefelter Syndrome?
Gynecomastia (breast development).
How does Klinefelter Syndrome affect testosterone levels and muscle mass?
Testosterone levels are low, and muscle mass tends to be reduced.
What cognitive effects are associated with Klinefelter Syndrome?
There is a predisposition for learning disabilities and a reduction in verbal IQ, typically 10 to 15 points lower than that of the affected person’s siblings.
Why is Klinefelter Syndrome often diagnosed later in life?
Due to its subtlety, it is often not diagnosed until after puberty and is sometimes first discovered in fertility clinics.
What is the most common known cause of pregnancy loss?
Chromosome abnormalities
What percentage of conceptions with chromosome abnormalities are lost before term?
At least 95%
What chromosome abnormality is thought to be the most common at conception but is rarely seen in live births?
Trisomy 16
What structural abnormalities are seen in approximately 1% of oocytes and 5% of sperm cells?
Structural chromosome abnormalities
What are structural chromosome abnormalities?
Alterations in chromosome structure that can involve the loss or gain of chromosome parts or changes in chromosome arrangement.
What can cause structural chromosome abnormalities?
Structural abnormalities can occur due to improper alignment of homologous chromosomes during meiosis, unequal crossover, or chromosome breakage during meiosis or mitosis.
What are clastogens?
Harmful agents that can increase the likelihood of chromosome breakage.
What is the term for the interchange of genetic material between nonhomologous chromosomes?
Translocation
What type of translocation involves a reciprocal exchange of segments between two nonhomologous chromosomes?
Reciprocal translocation
What type of translocation involves the fusion of two acrocentric chromosomes at their centromeres, resulting in a single chromosome?
Robertsonian translocation
Which type of translocation is most commonly associated with an increased risk of chromosomal abnormalities in offspring?
Robertsonian translocation
What happens during a reciprocal translocation?
Breaks occur in two different chromosomes, and the material is mutually exchanged.
What are the chromosomes called that result from a reciprocal translocation?
Derivative chromosomes
Why are carriers of reciprocal translocations usually unaffected?
They have a normal complement of genetic material.
What types of genetic material can the offspring of a carrier of a reciprocal translocation inherit?
The offspring can inherit normal genetic material, carry the translocation, or have duplications and deletions of genetic material.
What can result in the offspring of a person with a reciprocal translocation?
The offspring may have partial trisomy or partial monosomy and an abnormal phenotype.
What happens to the short arms of chromosomes during a Robertsonian translocation?
The short arms of two nonhomologous chromosomes are lost.
What occurs to the long arms of chromosomes in Robertsonian translocations?
The long arms fuse at the centromere to form a single chromosome.
Which chromosomes are involved in Robertsonian translocations?
Acrocentric chromosomes (13, 14, 15, 21, and 22).
Why are carriers of Robertsonian translocations phenotypically unaffected?
The short arms of these chromosomes are very small and contain no essential genetic material.
What is the karyotype designation for a male carrier of a Robertsonian translocation involving chromosomes 14 and 21?
45,XY,der(14;21)(q10;q10).
What can result from adjacent segregation during meiosis in a carrier of a Robertsonian translocation?
Gametes may be unbalanced, leading to trisomy or monosomy of the long arms of the involved chromosomes.
What is the expected percentage of live-born offspring with Down syndrome from a carrier of a Robertsonian translocation? In mothers? In fathers?
About 10%-15% for mothers and 1%-2% for fathers.
What is a terminal deletion?
A loss of genetic material including the chromosome’s tip after a single break.
What is an interstitial deletion?
A loss of genetic material between two breaks in a chromosome.
What happens when a gamete with a deletion unites with a normal gamete?
The zygote has one normal chromosome and one chromosome with the deletion.
What is cri-du-chat syndrome caused by?
A deletion of the distal short arm of chromosome 5.
What is the characteristic cry associated with cri-du-chat syndrome?
A distinctive cry that resembles a cat’s cry.
What chromosome deletion causes Wolf-Hirschhorn syndrome?
chromosome 4.
What is the role of high-resolution banding in detecting microdeletions?
It allows for the identification of smaller deletions that were previously undetectable.
What microdeletion of a chromosome is Prader-Willi syndrome associated with?
Chromosome 15q11-q13
Which chromosome microdeletion is associated with Angelman syndrome?
chromosome 15
What chromosome deletion is associated with Williams syndrome?
chromosome 7
What gene is crucial in the Williams syndrome critical region and what is its role?
The ELN gene, which encodes elastin and is important for the aortic wall.
How does the deletion size in Williams syndrome affect the phenotype?
Larger deletions encompass more genes and produce the full Williams syndrome phenotype, while smaller deletions may result in isolated features like SVAS.
What is a contiguous gene syndrome?
A condition caused by the deletion or duplication of a series of adjacent genes on a chromosome, such as in WAGR syndrome.
What chromosome deletion is WAGR syndrome associated with?
chromosome 11p
What causes the consistent size of deletions in microdeletion syndromes like Prader-Willi syndrome?
The presence of multiple low-copy repeats at the deletion boundaries promotes unequal crossing over.
What role do low-copy repeats play in microdeletion syndromes?
They promote unequal crossing over, leading to duplications and deletions of the chromosomal region bounded by these repeats.
What is the size of the deletion critical region in Prader-Willi syndrome?
Approximately 4 Mb.
What is a common consequence of rearrangements near chromosome telomeres?
They often result in genetic disease due to the high density of genes in these regions.
What is the most common subtelomeric rearrangement?
chromosome 1p36.
What is uniparental disomy?
A condition where one parent contributes two copies of a chromosome and the other parent contributes no copies.
What is the term for uniparental disomy when one parent contributes two copies of one homolog?
Isodisomy
What is the term for uniparental disomy when one parent contributes one copy of each homolog?
Heterodisomy
How can uniparental disomy of an imprinted chromosome cause diseases such as Prader-Willi syndrome?
It can cause the absence of active paternal genes in the imprinted region if two copies are inherited from the mother and none from the father.
What is a potential result of isodisomy in the offspring of a heterozygous parent?
It can result in autosomal recessive disease if the parent contributes two copies of the chromosome with a disease-causing mutation.
What is an example of a disease caused by uniparental disomy where the parent transmits two copies of the chromosome containing a mutation?
Cystic fibrosis
How can uniparental disomy arise in a trisomic conception?
It can arise if the embryo loses one of the extra chromosomes, resulting in two copies of the chromosome from one parent.
What is a mechanism by which uniparental disomy can occur in the early embryo?
It can occur due to mitotic errors, such as chromosome loss followed by duplication of the homologous chromosome.
What is a partial trisomy or duplication of genetic material?
It is a condition where extra genetic material is present, often seen in offspring of individuals with a reciprocal translocation or caused by unequal crossover during meiosis.
Why are duplications generally less severe than deletions?
Because a loss of genetic material usually has more serious consequences than an excess of genetic material.
What forms when deletions occur at both tips of a chromosome and the remaining ends fuse?
A ring chromosome.
What is the karyotype notation for a female with a ring X chromosome?
46,X,r(X).
What can happen to ring chromosomes during cell division?
They can often be lost, resulting in monosomy for the chromosome in some cells, leading to mosaicism.
What are two of the most common ring chromosomes described in humans?
Rings of chromosomes 14 and 22.
What happens during an inversion on a chromosome?
Two breaks occur on the chromosome, and the intervening fragment is reinserted at the original site but in inverted order.
What is the difference between a pericentric and a paracentric inversion?
A pericentric inversion includes the centromere, while a paracentric inversion does not involve the centromere.
Why do inversions rarely produce disease in the inversion carrier?
Because inversions are typically balanced structural rearrangements and do not usually result in a loss or gain of genetic material.
How can inversions affect meiosis and offspring?
Inversions can interfere with meiosis, leading to the formation of a loop during prophase I. Crossing over within this loop can result in duplications or deletions in the chromosomes of daughter cells.
What is the estimated frequency of people carrying an inversion?
About 1 in 1000 people.
What is an isochromosome?
A chromosome with two copies of one arm and no copies of the other.
What typically happens to isochromosomes of most autosomes?
They are usually lethal due to substantial alteration of genetic material.
Which isochromosomes are most commonly observed in live births?
Isochromosomes involving the X chromosome.
What condition is often associated with isochromosome Xq?
Turner syndrome
What phenotype can be observed with isochromosome 18q?
Edwards syndrome phenotype.
How can isochromosomes also be created aside from faulty division?
By Robertsonian translocations of homologous acrocentric chromosomes.
What chromosome alteration is consistently seen in patients with chronic myelogenous leukemia (CML)?
A reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome.
What is the Philadelphia chromosome characterized by?
A translocation of most of chromosome 22 onto the long arm of chromosome 9 and a small distal portion of 9q translocated to chromosome 22.
What gene is altered in CML due to the Philadelphia chromosome?
ABL proto-oncogene
What type of cancer is associated with a reciprocal translocation between chromosomes 8 and 14?
Burkitt lymphoma.
How many different chromosome rearrangements have been observed in cancer, and how does this help in treatment?
More than 100 different rearrangements in over 40 types of cancer. Identifying these rearrangements leads to more accurate prognosis and better therapy.
What additional factor can increase chromosome breakage in patients with Fanconi anemia?
Exposure to certain alkylating agents.
What is a notable cytogenetic feature of Bloom syndrome?
A high incidence of somatic cell sister chromatid exchange.
What common underlying issue is thought to contribute to chromosome instability syndromes?
Faulty DNA replication or repair.
What is the relationship between chromosome instability syndromes and cancer risk?
All chromosome instability syndromes are associated with a significant increase in cancer risk.
Which type of inheritance, males and females, are equally likely to transmit the trait to their offspring, and it shows a vertical transmission?
Autosomal Dominant
Which factors that affects expression of disease-causing genes refers to genes that exert affects on multiple aspects of physiology or anatomy?
Pleiotropy
In autosomal dominant diseases frequently affected offspring are produced by the union of an unaffected parent with an affected heterozygote. In this scenario, what will be the probability for children to be heterozygote?
0.5
In which type of inheritance do affected fathers cannot transmit the trait to their sons but can transmit the trait to all their daughters and it shows a horizontal transmission?
X linked recessive
Asthma is a multifactorial and polygenic disease characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Studies of twins and of families of asthmatic individuals demonstrate a range of heritability of asthma from 25 to 80 percent. How will be the recurrence risk of asthma?
Affected by the severity of asthma in the family members
What is inflammation?
A protective response that delivers leukocytes and molecules of host defense to sites of infection and cell damage.
Why is inflammation important?
It helps rid the body of the cause of cell injury and the consequences of injury, such as necrotic cells and tissues.
