Chapter 6 Flashcards
Translocation
-a chromosomal abnormality in which all or part of a chromosome is transferred to another nonhomologous chromosome.
-(A nonhomologous chromosome is not part of the normal chromosome pair. For example, one number 13 chromosome and one number 15 chromosome are a nonhomologous pair, whereas two number 13s or two number 15s are homologous pairs.)
-The actual location of the genetic material is less important for normal growth, development, and function.
- A translocation can be balanced or unbalanced.
- a translocation is first described by the rest of the karyotype and then is described by a lowercase t and the chromosomes involved. For example, a female with a translocation of a number 21 chromosome onto a number 14 chromosome would be described as 45,XX,-14,-21,t(l4q;21q).
-If the translocation involves only parts of chromosomes rather than whole chromosomes, the breakpoints also are listed (if known). For example, a male with a translocation between 12q14 and 22q21 would be described as 46, XY,t(l2;22)(q14;q21).
-When the location of some genetic material is translocated from one chromosome to another, normal development can occur (so long as the correct amount of DNA is present), but reproductive issues often arise in the mature individual.
Balanced translocation
-the right amount of DNA is present (no more and no less), but not all the DNA is located in its customary place.
-no specific risk exists either for abnormal development or miscarriage of this individual as a fetus. This individual has the translocation in all cells, and neither phenotype nor physiologic function is affected.
-The two types of common balanced rranslocations are Robertsonian and reciprocal translocations.
[balanced translocation]
Robertsonian translocation
-a specific type of balanced translocation created by the fusion of the entire long arms (q arms) of two acrocentric chromosomes with the loss of the short arms (p arms).
-the DNA of the centro meres of two acrocentric chromosomes attract each other.
-Because the very small p arms of acrocentric chromosomes carry no significant genetic material, their loss does not affect development and normal phenotypic appearance.
-person with such a translocation has a karyotype with only 45 chromosomes
[balanced translocation]
Reciprocal translocations
-balanced translocation in which segments of two non- homologous chromosomes break and are equally exchanged.
-can occur between any two chromosomes, not just between acrocentric chromosomes.
- Because genetic material is neither gained nor lost, the translocation is balanced, and the person’s development and normal phenotypic appearance are not affected.
-because this type of translocation involves only chromosome segments rather than whole chromosomes, the person’s karyotype shows 46 chromosomes
- individual is considered a translocation carrier only if the translocation is present in all cells.
Unbalanced translocation.
- when a child inherits more than or less than two copies of a chromosome or part of a chromosome from a parent.
- results in abnormal anatomic development and physiologic function.
- can lead to trisomy, monosomy, and other chromosomal disorders.
[common chromosomal disorders]
Trisomy
-Inheritance of an extra copy of one chromosome
-Most commonly, trisomies occur when one pair of chromosomes fails to separate properly during meiosis, a problem termed nondisjunction.
-most common disorders of trisomy are trisomy 21, 18, and 13
-The presence of extra sex chromosomes, especially the X chromosome, also is relatively common
-can also occur due to Robertsonian translocation or unbalanced translocation
- The developmental and functional consequences of trisomy are the same regardless of the origin of the extra chromosome material.
-ex., Down syndrome, or trisomy 21, results from the inheritance of three copies of chromosome 21
[common chromosomal disorders]
Trisomy 21
-Down syndrome
-extra number 21 chromosome in all or most of a person’s cells. ‘
-Developmental and functional abnormalities
[common chromosomal disorders]
Trisomy 18
-Edward syndrome
-extra number 18 chromosome in all or most of a person’s cells
-Severe developmental and functional abnormalities result from having three copies of all or most alleles on chromosome 18
-most affected children are stillborn.
-affects more females than males
-Although very few children with trisomy 18 survive childhood, and they have greatly reduced intellectual capacity, some are able to interact with family members. Skills such as social smiling, rolling over, and limited self-feeding have been reported
[common chromosomal disorders]
Abnormalities Associated With Common Trisomic Conditions
Table 6-1
[common chromosomal disorders]
Trisomy 13
-Patau syndrome
-extra number 13 chromosome in all or most of a person’s cells
-Severe developmental and functional abnormalities result from having three copies of all or most alleles on chromosome 13, and both stillbirths and early neonatal deaths are common.
-Some of the phenotypic features of trisomy 13 resemble those of trisomy 18, although others are unique to the disorder.
[common chromosomal disorders]
Monosomy
-Inheriting only one chromosome of a pair
-The most common cause of this condition is thought to be nondisjunction during meiosis.
-Although, in theory, monosomy can occur among any pair of chromosomes, the only common incidence of monosomy is Turner syndrome, in which a female is missing one of the X chromosomes and has a karyotype of 45,X (see Chapter 7).
-In addition, a few cases of monosomy 21 have been reported.
[common chromosomal disorders]
Triploidy
-rare
-inheritance of an extra copy of each chromosome, resulring in a person who has 69 chromosomes per cell instead of 46.
-usually lethal, spontaneous miscarriage
-common cause of triploidy conceptions is the ferrilizarion of one ovum by two sperm.
-Less commonly, an ovum may fail to complete meiosis and have 46 chromosomes.
WAGR Syndrome
-WAGR syndrome stands for Wilms tumor, aniridia, genitourinary malformations, and intellectual disability (formerly referred to as retardation).
-Children born without an iris (aniridia) were noted to share other consistent clinical features, including severely reduced cognitive function (intellectual disability) and a variety of genitourinary (GU) tract malformations.
-The GU malformations can be as mild as first-degree hypospadias, in which the urethral opening on the penis is located off to one side rather than centered, or as severe as complete exstrophy of the bladder.
-About 40% of children expressing these symptoms at birth went on to develop a specific type of kidney cancer called Wilms tumor (nephroblastoma), usually before age 5.
Genomic imprinting
-an epigenetic event in which a gene (or gene allele) is inactivated by means other than mutation, so the DNA sequence of the gene remains normal, but irs expression is inhibited.
-an epigenetic event in which a gene (or gene allele) is inactivated by means other than mutation, so the DNA sequence of the gene remains normal, but irs expression is inhibited.
-an epigenetic event in which a gene (or gene allele) is inactivated by means other than mutation, so the DNA sequence of the gene remains normal, but its expression is inhibited.
uniparental disomy (UPD)
- both chromosomes of a pair come from just onep[ parent.
Summary
Most individuals are genetically “normal,” although very few humans are genetically perfect. Rearrangements of genetic material occur frequently during the process of gametogenesis. Fertilization and conception occur more frequently than does a live birth or even a detectable pregnancy. Some conceptions fail to develop beyond the earliest stages, and still others fail to implant in the uterus. Even when implantation occurs, pregnancy loss during the first trimester is significant. Both random chromosome changes and heritable chromosome changes account for many of these losses.
• Although chromosome structure is temporary, the double-Stranded DNA that makes up the chromosome is a permanent section of the roral DNA within one cell’s nucleus.
• Individuals who have balanced chromosomal translocations do not have abnormal development or phe- notypes because of the translocation; however, the translocation does pose reproductive consequences.
• Individuals who have unbalanced chromosomal translocations do have abnormal development and
phenotypes because of the translocation.
• Robertsonian translocarions occur only between acrocentric chromosomes.
• The most common chromosomal abnormality among live-born infants is trisomy 21 (Down syndrome).
• Many specific features are associated with various trisomies; however, few affected individuals express
every feature.
• Monosorny of autosomal chromosomes appears to be lethal.
• Individuals with Angelman syndrome and individuals who have Prader-Willi syndrome have the same
chromosomal deletion, but the parental origin of the chromosome with the deletion differs.
Mosaicism
-condition in which two (or more) different karyotypes are consistently present in one individual.
-This means that some cells have an abnormal karyotype, and others have a normal karyotype.
- Why do balanced translocation carriers have normal development and function?
a. The extra chromosomal material is present only in germ cells and not in somatic cells.
b. The extra chromosomal material is present only in somatic cells and not in germ cells.
c. They have the correct amount of chromosomal material, and only its location is abnormal.
d. Their translocations involve only DNA noncoding regions, with no involvement of actual gene-coding regions.
C
- Which chromosomes are most likely to be involved in a Robertsonian translocation?
a. An X chromosome and a Y chromosome
b. Chromosome 21 and chromosome 11
c. Chromosome 21 and the X chromosome
d. Chromosome 13 and chromosome 14
D
- What is the difference between triploidy and trisomy?
a. Triploidy involves an extra copy of every chromosome, and trisomy involves an extra copy of only
one chromosome.
b. Trisomy involves an extra copy of every chromosome, and triploidy involves an extra copy of only
one chromosome.
c. Triploidies are maternally derived, and trisomies are paternally derived.
d. Trisomies are fatal more frequently than are triploidies.
A
- Which clinical feature is a common finding for infants with trisomy 21, trisomy 18, and trisomy 13?
a. Rocker-bottom feet
b. Single palmar crease
c. Small, close-set eyes
d. Cleft lip (with or without cleft palate)
B
- What is the risk for a woman with Down syndrome to produce a child with Down syndrome when impregnated by a man who has normal chromosome numbers?
a. No chance
b. Less than 50%
c. Greater than 50%
d. Approaching 100%
B
- A friend of yours is concerned that he may be a “carrier” for Down syndrome because both he and his sister have a “simian” crease on one hand. What is your best action or response?
a. Ask him how many people in his family have been diagnosed with Down syndrome.
b. Tell him the simian crease is only diagnostic if it is present on both hands.
c. Remind him that Down syndrome “carriers” must be homologous to transmit the disorder.
d. Explain that chromosomally normal people often have one or more features associated with Down
syndrome.
D
