Term
| Define clinical cytogenetics |
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Definition
| the study of chromosome number, structure, and inheritance, as applied to medical genetics |
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Term
| Chromosome are present in nearly _____% of live births, in about _____% of pregnancies in women older than 35 who undergo prenatal diagnosis, and in fully ________ of all spontaneous first-trimester abortions |
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Definition
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Term
| What are 6 general clinical indications for chromosome analysis? |
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Definition
1. problems of early growth development
2. stillbirth and neonatal death (10% of newborns are so bc of a chromosomal disorder)
3. fertility problems (5% of couples: man or woman has chromosome abnormality
4. family hx
5. neoplasia (virtually all cancers are associated with one or more chromosomal abnormalities)
6. pregnancy in a woman of advanced age |
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Term
| What are three methods for analyzing human chromosomes, which can see the the smallest abnormalities? |
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Definition
-karyotype (G-banding)
-FISH (fluorescence in situ hybridization)
-comparative genome hybridization (can see very small abnormalities) |
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Term
| Where do microtubule fibers attach to a chromosome during cell division? |
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Definition
| the centromere. it also gives the chromosome its characteristic shape. |
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Term
| Define the three terms used to describe centromere location |
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Definition
-Metacentric: chromosome that has a centrally placed centromere
-Submetacentric: a chromosome whose centromere is placed closer to to one end than the other
-acrocentric: a chromosome whose centromere is placed very close to, but not at, one end |
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Term
| Chromosomes in which stage of mitosis are used for analyzing? |
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Definition
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Term
| What are three criteria used to identify metaphase chromosomes? |
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Definition
-size
-centromere location
-banding |
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Term
| What is the satellite sequence of an acrocentric chromosome? |
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Definition
| they are repeat sequences of DNA that do not have any genes |
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Term
| What are the sex chromosomes in humans? |
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Definition
| The X and Y chromosomes that are involved in sex determination |
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Term
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Definition
chromosomes other than the sex chromosomes
-chromosomes 1-22 are autosomes |
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Term
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Definition
| a complete set of chromosomes from a cell that has been photographed during metaphase of mitosis and arranged in a standard sequence |
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Term
| Almost any cell with a _______ can be used to make a karyotype. What cells does this exclude? |
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Definition
-nucleus (e.g. lymphocytes, skin cells, cells from biopsies, tumor cells)
-NOT mature RBCs |
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Term
| What are two procedures that are preformed to sample cells before birth? |
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Definition
-amniocentesis
-chorionic villus sampling (CVS) |
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Term
| What is used when making a karyotype to stop mitosis of the cells in metaphase? |
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Definition
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Term
| What 4 pieces of information can be obtained from a karyotype? |
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Definition
-number of chromosomes
-sex chromosome content
-presence or absence of individual chromosomes
-nature and extent of large structural abnormalities |
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Term
| What are two aspects of FISH that make it preferable to G-banding? |
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Definition
-allows us to look for the presence or absence of a specific DNA sequence
-allows us to evaluate the number or organization of chromosomal regions with much greater resolution than G-banding |
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Term
| CGH can assess the relative copy number of genomic DNA sequences in a genome-wide manner, but what can it not tell you? |
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Definition
| whether or not they have ben translocated or rearranged from their normal position in the genome |
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Term
| What are the two major types of chromosome abnormalities? |
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Definition
-abnormalities of chromosome number (occurs with the greatest frequency)
-abnormalities of chromosome structure |
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Term
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Definition
| any chromosome number other than the normal 46 |
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Term
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Definition
| an exact multiple of the haploid chromosome number (n; 23) |
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Term
| Define polyploid (tirploid and tetraploid, too) |
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Definition
three or more multiples of the haploid chromosome number
-triploid: (3n; 69): is three times the the haploid number (main way for this to happen is if one egg is fertilized by two sperm)
-tetraploid: (4n;92): four times the haploid number (main way for this to happen is if after the sperm fertilizes the egg, when it is a zygote, in early cell division the DNA gets replicated but the cell fails to divide) |
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Term
| Define aneuploid (monosomy and trisomy, too) |
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Definition
an abnormal chromosome number due to an extra or missing chromosome; not an exact multiple of the haploid set
-monosomy (2n; 45) is only one of a particular chromosome
-trisomy (2n; 47) is three of a particular chromosome |
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Term
| How often is polyploidy seen in live births? |
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Definition
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Term
| What is the most common type of clinically significant chromosome abnormality in humans? |
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Definition
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Term
| Close to ________ of all conceptions are aneuploidy |
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Definition
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Term
| What physical characteristic(s) is aneuploidy always associated with |
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Definition
| -abnormal physical or mental development or both |
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Term
| Most aneuploid patients either have _________ or __________ |
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Definition
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Term
| What is the most common mechanism for aneuploidy? |
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Definition
| chromosomal nondisjunction during maternal meiosis 1 |
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Term
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Definition
| the failure of homologous chromosomes to separate properly during meiosis |
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Term
| autosomal monosomy is a _______ condition |
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Definition
| lethal (eliminated early in development, spontaneous abortion) |
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Term
| What are the three types of autosomal trisomy that can result in live births? What is each associated with? |
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Definition
13, 18, 21
-growth retardation, mental retardation, and multiple congenital abnormalities |
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Term
| What is another name for trisomy 13? What is it's inheritance, genetic etiology, and frequency? |
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Definition
-Patau syndrome (47, +13)
-I: chromosomal
GE: trisomy for chromosome 13 due to nondisjunction in maternal meiosis 1
F: 1 in 22,700 live births |
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Term
| What are some common clinical features of Patau Syndrome? |
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Definition
-low birth weight
-cleft lip and palate
-ocular abnormalities
-polydactyly
-rocker-bottom feet
-anomalies of internal organs including heart, brain, and kidneys |
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Term
| What is the prognosis for baby born with Patau syndrome? |
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Definition
| most of these babies die before they are born, small amount live for about 3 days, and in very rare cases they could live to be about 1 year old |
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Term
| For couples who have had a child with Patau syndrome, what is the recurrence risk? How than it be detected before birth? |
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Definition
1%
prenatal chromosomal analysis |
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Term
| What is another name for trisomy 18? Inheritance? Genetic Etiolgy? Frequency? |
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Definition
-Edwards syndrome (47, +18)
-I: chromosomal
-GE: trisomy for chromosome 18 due to nondisjunction in maternal meiosis I
-F: 1 in 7,500 live births |
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Term
| What are some common clinical features in a baby with Edwards syndrome? |
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Definition
-multiple congenital anomalies: low birth weight, prominent occiput, tightly clenched fingers, low -set and malformed ears, rocker bottom feet
-internal organ malformations: heart and brain |
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Term
| What is the prognosis for children with Edwards syndrome? |
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Definition
-most die in infancy or childhood (many within the first month)
-only 5-10% live past their first year |
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Term
| For couples who have had a child with Edwards syndrome, what is the recurrence risk? How can it be detected before birth? |
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Definition
1%
prenatal chromosomal analysis |
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Term
| What is another name for trisomy 21? Inheritance? Genetic Etiology? Frequency? |
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Definition
-Down Syndrome (47, +21)
-I: chromosomal
-GE: mostly due to nondisjunction in maternal meiosis 1. 5% of cases due to Robertsonian translocation, 2% are mosaic for a trisomy 21 cell line
F: 1 in 830 live births |
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Term
| What is a robertsonian translocation? |
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Definition
| a translocation in which the centromeres of two non-homologous chromosomes fuse and the short arms are lost |
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Term
A robertsonian translocation between which two chromosomes results in down syndrome?
In effect this makes DS a heritable genetic disorder, which could be potentially present in one in ______ offspring |
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Definition
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Term
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Definition
| the presence of at least two cell lines that differ genetically, but are derived from the same zygote. |
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Term
| Can mosaicism be present in both somatic and germ line cells? |
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Definition
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Term
| what is mosaicism commonly caused by? |
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Definition
| nondisjunction in an early post zygotic mitotic division |
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Term
| When a person has a chromosome abnormality, the abnormality is usually present in all of his or her cells. However, when two or more different chromosome complements are present within an individual, this is known as _____________ |
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Definition
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Term
| What are some clinical features of down syndrome? |
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Definition
-hypotonic at birth
-congenital anomalies: cardiac and GI
-facial features: flat occiput, up-slanting palpebral fissures, furrowed tongues, short fingers and toes
-cognitive development tends to be delayed, though is variable |
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Term
| People with down syndrome are at a higher risk of what during childhood? what during infancy? what as an adult? |
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Definition
-respiratory infection during childhood
-leukemia and transient leukemoid reactions in infancy
-early onset Alzheimer's disease as adults |
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Term
| What is the leading risk factor for trisomy? |
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Definition
maternal age
(for trisomy 21, 94% of nondisjunctions occur in the mother, 6% in the father) |
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Term
| from what do structural rearrangements of chromosomes result? |
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Definition
| -chromosome breakage, followed by reconstitution in an abnormal combination |
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Term
| WHat are the two classifications of chromosomal rearrangements? |
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Definition
-unbalanced: additional or missing chromosomal material
-balanced: normal complement of material |
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Term
| In unbalanced chromosomes, ___________ is likely to be abnormal. Is this the same for balanced rearrangements? |
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Definition
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Term
| What are some examples of unbalanced rearrangements? |
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Definition
deletions
duplications
isochromosomes
dicentric chromosomes |
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Term
| what are some examples of balanced rearrangements? |
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Definition
inversions
reciprocal translocations
robertsonian translocations
insertions |
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Term
| To be stable, a rearranged chromosome must have _______ centromere and _______ telomeres |
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Definition
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Term
| Two consequences of deletions are haploinsuffiency and contiguous gene syndrome. Define each of these. |
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Definition
-haploinsufficiency: the inability of one copy of a gene to perform the function of two normal copies of the gene
-contiguous gene syndrome: a syndrome with a phenotype that is cause by deletion of multiple, neighboring genes |
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Term
| Define genomic imprinting. |
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Definition
| differences in gene expression between the allele inherited from the mother and the allele inherited from the father |
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Term
| What is genomic imprinting most often caused by? |
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Definition
| methylation of cytosine. This is a methylation in the promoter region of the gene that silences gene expression without altering DNA sequence. THis is a epigenetic modification, NOT a mutation |
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Term
| Define paternal and maternal imprinting. |
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Definition
-Paternal= the allele inherited from the father is not expressed in the offspring
-Maternal= the allele inherited from the mother is not expressed in the offspring |
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Term
| Imprinting occurs during _________, before fertilization, and marks certain genes as having come from the mother or father. It persists into ___________ |
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Definition
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Term
| Is genomic imprinting reversible? why or why not? |
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Definition
| Yes. This is bc a paternally derived allele inherited by a female must be converted in her germ line so that she can then pass it on with a maternal imprint to her offspring (and vice versa) |
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Term
| What is uniparental disomy? |
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Definition
| A condition in which both copies of a chromosome are inherited from a single parent |
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Term
| What is the inheritance of prader-willi syndrome? |
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Definition
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Term
| what are the possible genetic etiologies of prader-willi syndrome? |
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Definition
*it is associated with defects based on genomic imprinting
-approx. 70% have a deletion of the paternal 15q11.2-q13 region
-about 25% have uniparental disomy, with two maternal copies of chromosome 15
-small proportion has a mutation of the imprinting center on chromosome 15 |
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Term
| What is the frequency of prader-willi syndrome |
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Definition
| 1 in 10,000 to 15,000 live births |
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Term
| What are some of the clinical features of prader willi syndrome? |
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Definition
-at birth: hypotonic, lethargic, difficulty feeding
-childhood: eat too much, obesity, developmental delay, behavioral disturbances
-distinctive facial features and short stature is common |
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Term
-recurrence of micro deletion or uniparental disomy in siblings of a pro band are ________
-imprinting center mutations can be transmitted as ________ traits |
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Definition
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Term
| What is the inheritance of angelman syndrome? |
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Definition
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Term
| What is the genetic etiology of angelman syndrome? |
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Definition
*associated with defects based on genomic imprinting
-approx 70% have a deletion of the maternal 15q11.2-q13 region
-about 5% have uniparental disomy, with two paternal copies of chromosome 15
-about 5% have small deletions of the imprinting center on chromosome 15
**About 10% have a mutation in the ubiquitin-protein ligase E3A (UBE3A) gene, which resides in this region of chromosome 15 and is imprinted |
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Term
| What is the frequency of angel man syndrome? |
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Definition
| 1 in 12,000 to 20,000 live births. |
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Term
| What are the clinical features of angelman syndrome? |
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Definition
-severe developmental delay
-seizures and hyperactivity is common
-walking is delayed, or may not occur at all, and for those who do walk gait is stiff and clumsy |
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Term
| Imprinting center or UBE3A mutations can be transmitted as ______ traits |
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Definition
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Term
| Complete monosomies are generally not viable except for monosomy ______ |
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Definition
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Term
| For which chromosomes are complete trisomies viable? |
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Definition
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Term
| Phenotype in partial aneusomies (deletions, duplications) depends on what three things? |
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Definition
- the size of the unbalanced segment
-whether the imbalance is monosomic or trisomic
-which regions of the genome are affected and which genes are involved |
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Term
| WHat is the risk of birth defect in a pericentric inversion? |
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Definition
| increases with size of the inversion |
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Term
| what is the risk of abnormal phenotype in paracentric inversions? |
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Definition
| very low risk of abnormal phenotype |
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