Chromosomal Basis of Inherited Disorders Quiz

PDF page 544: trisomy otherwise diploid genotype in which one entire chromosome is duplicated X inactivation condensation of X chromosomes into Barr bodies during embryonic development in females to compensate for the double genetic dose

PDF page 537: An individual with the appropriate number of chromosomes for their species is called euploid; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid, a term that includes monosomy (loss of one chromosome) or trisomy (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype (Figure 13.7).

PDF page 534: prevent errors, the processes are not perfect. One example is the failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or meiosis II (a phenomenon referred to as nondisjunction). This results in gametes with too many or too few chromosomes. Disorders in chromosome number (aneuploidy) are typically lethal to the embryo, although a few trisomic genotypes are viable (e.g., Down syndrome). Because of X inactivation, aberrations in sex chromosomes typically have milder phenotypic effects (e.g., Turner syndrome) than aneuploidy. Sometimes segments of chromosome are duplicated, deleted, or rearranged by inversion or translocation. These aberrations can result in problematic phenotypic effects. Diagnostic testing can detect many of these chromosomal disorders in individuals well before birth, resulting in medical, ethical, and civic issues, such as the right to privacy. A condition in which an organism has more than the normal number of chromosome sets (two for diploid species) is called polyploidy. Polyploidy resulting in odd numbers of chromosomes is rare because it results in sterile organisms. One set of chromosomes has no pair so meiosis cannot proceed normally. In contrast, polyploidy resulting in even chromosome numbers is very common in the plant kingdom. Polyploid plants tend to be larger and more robust than individuals with the normal number of chromosomes.

PDF page 539: Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome. Rather than a gain or loss of autosomes, variations in the number of sex chromosomes are associated with relatively mild effects. In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells (relative to trillions in the newborn), one X chromosome in each cell inactivates by tightly condensing into a quiescent (dormant) structure called a Barr body. The chance that an X chromosome (maternally or paternally derived) is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that one will have the same inactive X chromosome or Barr body. By this process, females compensate for their double genetic dose of X chromosome. In so-called “tortoiseshell” cats, embryonic X inactivation is observed as color variegation (Figure 13.9). Females that are heterozygous for an X-linked coat color gene will express one of two different coat colors over different regions of their body, corresponding to whichever X chromosome is inactivated in the embryonic cell progenitor of that region.

PDF page 537: An individual with the appropriate number of chromosomes for their species is called euploid; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid, a term that includes monosomy (loss of one chromosome) or trisomy (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype (Figure 13.7).

PDF page 540: utero. Several errors in sex chromosome number have been characterized. Individuals with three X chromosomes, called triplo- X, are phenotypically female but express developmental delays and reduced fertility. The XXY genotype, corresponding to one type of Klinefelter syndrome, corresponds to phenotypically male individuals with small testes, enlarged breasts, and reduced body hair. More complex types of Klinefelter syndrome exist in which the individual has as many as five X chromosomes. In all types, every X chromosome except one undergoes inactivation to compensate for the excess genetic dosage. This can be seen as several Barr bodies in each cell nucleus. Turner syndrome, characterized as an X0 genotype (i.e., only a single sex chromosome), corresponds to a phenotypically female individual with short stature, webbed skin in the neck region, hearing and cardiac impairments, and sterility.

PDF page 535: The isolation and microscopic observation of chromosomes forms the basis of cytogenetics and is the primary method by which clinicians detect chromosomal abnormalities in humans. A karyotype is the number and appearance of chromosomes, and includes their length, banding pattern, and centromere position. To obtain a view of an individual’s karyotype, cytologists photograph the chromosomes and then cut and paste each chromosome into a chart, or karyogram, also known as an ideogram (Figure 13.5).

PDF page 544: aneuploid individual with an error in chromosome number; includes deletions and duplications of chromosome segments autosome any of the non-sex chromosomes centimorgan (cM) (also, map unit) relative distance that corresponds to a recombination frequency of 0.01 Chromosomal Theory of Inheritance theory proposing that chromosomes are the vehicles of genes and that their behavior during meiosis is the physical basis of the inheritance patterns that Mendel observed chromosome inversion detachment, 180° rotation, and reinsertion of a chromosome arm euploid individual with the appropriate number of chromosomes for their species homologous recombination process by which homologous chromosomes undergo reciprocal physical exchanges at their arms, also known as crossing over karyogram photographic image of a karyotype karyotype number and appearance of an individuals chromosomes; includes the size, banding patterns, and centromere position monosomy otherwise diploid genotype in which one chromosome is missing nondisjunction failure of synapsed homologs to completely separate and migrate to separate poles during the first cell division of meiosis nonparental (recombinant) type progeny resulting from homologous recombination that exhibits a different allele combination compared with its parents paracentric inversion that occurs outside of the centromere parental types progeny that exhibits the same allelic combination as its parents pericentric inversion that involves the centromere polyploid individual with an incorrect number of chromosome sets recombination frequency average number of crossovers between two alleles; observed as the number of nonparental types in a population of progeny translocation process by which one segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome

PDF page 541: in nature as a result of mechanical shear, or from the action of transposable elements (special DNA sequences capable of facilitating the rearrangement of chromosome segments with the help of enzymes that cut and paste DNA sequences). Unless they disrupt a gene sequence, inversions only change the orientation of genes and are likely to have more mild effects than aneuploid errors. However, altered gene orientation can result in functional changes because regulators of gene expression could be moved out of position with respect to their targets, causing aberrant levels of gene products. An inversion can be pericentric and include the centromere, or paracentric and occur outside of the centromere (Figure 13.11). A pericentric inversion that is asymmetric about the centromere can change the relative lengths of the chromosome arms, making these inversions easily identifiable.

PDF page 544: aneuploid individual with an error in chromosome number; includes deletions and duplications of chromosome segments autosome any of the non-sex chromosomes centimorgan (cM) (also, map unit) relative distance that corresponds to a recombination frequency of 0.01 Chromosomal Theory of Inheritance theory proposing that chromosomes are the vehicles of genes and that their behavior during meiosis is the physical basis of the inheritance patterns that Mendel observed chromosome inversion detachment, 180° rotation, and reinsertion of a chromosome arm euploid individual with the appropriate number of chromosomes for their species homologous recombination process by which homologous chromosomes undergo reciprocal physical exchanges at their arms, also known as crossing over karyogram photographic image of a karyotype karyotype number and appearance of an individuals chromosomes; includes the size, banding patterns, and centromere position monosomy otherwise diploid genotype in which one chromosome is missing nondisjunction failure of synapsed homologs to completely separate and migrate to separate poles during the first cell division of meiosis nonparental (recombinant) type progeny resulting from homologous recombination that exhibits a different allele combination compared with its parents paracentric inversion that occurs outside of the centromere parental types progeny that exhibits the same allelic combination as its parents pericentric inversion that involves the centromere polyploid individual with an incorrect number of chromosome sets recombination frequency average number of crossovers between two alleles; observed as the number of nonparental types in a population of progeny translocation process by which one segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome

PDF page 539: Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome. Rather than a gain or loss of autosomes, variations in the number of sex chromosomes are associated with relatively mild effects. In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells (relative to trillions in the newborn), one X chromosome in each cell inactivates by tightly condensing into a quiescent (dormant) structure called a Barr body. The chance that an X chromosome (maternally or paternally derived) is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that one will have the same inactive X chromosome or Barr body. By this process, females compensate for their double genetic dose of X chromosome. In so-called “tortoiseshell” cats, embryonic X inactivation is observed as color variegation (Figure 13.9). Females that are heterozygous for an X-linked coat color gene will express one of two different coat colors over different regions of their body, corresponding to whichever X chromosome is inactivated in the embryonic cell progenitor of that region.

PDF page 539: Figure 13.9 In cats, the gene for coat color is located on the X chromosome. In the embryonic development of female

PDF page 534: prevent errors, the processes are not perfect. One example is the failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or meiosis II (a phenomenon referred to as nondisjunction). This results in gametes with too many or too few chromosomes. Disorders in chromosome number (aneuploidy) are typically lethal to the embryo, although a few trisomic genotypes are viable (e.g., Down syndrome). Because of X inactivation, aberrations in sex chromosomes typically have milder phenotypic effects (e.g., Turner syndrome) than aneuploidy. Sometimes segments of chromosome are duplicated, deleted, or rearranged by inversion or translocation. These aberrations can result in problematic phenotypic effects. Diagnostic testing can detect many of these chromosomal disorders in individuals well before birth, resulting in medical, ethical, and civic issues, such as the right to privacy. A condition in which an organism has more than the normal number of chromosome sets (two for diploid species) is called polyploidy. Polyploidy resulting in odd numbers of chromosomes is rare because it results in sterile organisms. One set of chromosomes has no pair so meiosis cannot proceed normally. In contrast, polyploidy resulting in even chromosome numbers is very common in the plant kingdom. Polyploid plants tend to be larger and more robust than individuals with the normal number of chromosomes.

PDF page 538: An individual with more than the correct number of chromosome sets (two for diploid species) is called polyploid. For instance, fertilization of an abnormal diploid egg with a normal haploid sperm would yield a triploid zygote. Polyploid animals are extremely rare, with only a few examples among the flatworms, crustaceans, amphibians, fish, and lizards. Polyploid animals are sterile because meiosis cannot proceed normally and instead produces mostly aneuploid daughter cells that cannot yield viable zygotes. Rarely, polyploid animals can reproduce asexually by haplodiploidy, in which an unfertilized egg divides mitotically to produce offspring. In contrast, polyploidy is very common in the plant kingdom, and polyploid plants tend to be larger and more robust than euploids of their species (Figure 13.8).

PDF page 540: In addition to the loss or gain of an entire chromosome, a chromosomal segment may be duplicated or lost. Duplications and deletions often produce offspring that survive but exhibit physical and mental abnormalities. Duplicated chromosomal segments may fuse to existing chromosomes or may be free in the nucleus. Cri-du-chat (from the French for “cry of the cat”) is a syndrome associated with nervous system abnormalities and identifiable physical features that result from a deletion of most of 5p (the small arm of chromosome 5) (Figure 13.10). Infants with this genotype emit a characteristic high-pitched cry on which the disorder’s name is based.

PDF page 537: An individual with the appropriate number of chromosomes for their species is called euploid; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid, a term that includes monosomy (loss of one chromosome) or trisomy (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype (Figure 13.7).

PDF page 538: Figure 13.7 The incidence of having a fetus with trisomy 21 increases dramatically with maternal age.

PDF page 542: Translocations A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome. Translocations can be benign or have devastating effects depending on how the positions of genes are altered with respect to regulatory sequences. Reciprocal translocations result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information (Figure 13.13).

PDF page 544: aneuploid individual with an error in chromosome number; includes deletions and duplications of chromosome segments autosome any of the non-sex chromosomes centimorgan (cM) (also, map unit) relative distance that corresponds to a recombination frequency of 0.01 Chromosomal Theory of Inheritance theory proposing that chromosomes are the vehicles of genes and that their behavior during meiosis is the physical basis of the inheritance patterns that Mendel observed chromosome inversion detachment, 180° rotation, and reinsertion of a chromosome arm euploid individual with the appropriate number of chromosomes for their species homologous recombination process by which homologous chromosomes undergo reciprocal physical exchanges at their arms, also known as crossing over karyogram photographic image of a karyotype karyotype number and appearance of an individuals chromosomes; includes the size, banding patterns, and centromere position monosomy otherwise diploid genotype in which one chromosome is missing nondisjunction failure of synapsed homologs to completely separate and migrate to separate poles during the first cell division of meiosis nonparental (recombinant) type progeny resulting from homologous recombination that exhibits a different allele combination compared with its parents paracentric inversion that occurs outside of the centromere parental types progeny that exhibits the same allelic combination as its parents pericentric inversion that involves the centromere polyploid individual with an incorrect number of chromosome sets recombination frequency average number of crossovers between two alleles; observed as the number of nonparental types in a population of progeny translocation process by which one segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome

PDF page 537: An individual with the appropriate number of chromosomes for their species is called euploid; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid, a term that includes monosomy (loss of one chromosome) or trisomy (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype (Figure 13.7).

PDF page 544: aneuploid individual with an error in chromosome number; includes deletions and duplications of chromosome segments autosome any of the non-sex chromosomes centimorgan (cM) (also, map unit) relative distance that corresponds to a recombination frequency of 0.01 Chromosomal Theory of Inheritance theory proposing that chromosomes are the vehicles of genes and that their behavior during meiosis is the physical basis of the inheritance patterns that Mendel observed chromosome inversion detachment, 180° rotation, and reinsertion of a chromosome arm euploid individual with the appropriate number of chromosomes for their species homologous recombination process by which homologous chromosomes undergo reciprocal physical exchanges at their arms, also known as crossing over karyogram photographic image of a karyotype karyotype number and appearance of an individuals chromosomes; includes the size, banding patterns, and centromere position monosomy otherwise diploid genotype in which one chromosome is missing nondisjunction failure of synapsed homologs to completely separate and migrate to separate poles during the first cell division of meiosis nonparental (recombinant) type progeny resulting from homologous recombination that exhibits a different allele combination compared with its parents paracentric inversion that occurs outside of the centromere parental types progeny that exhibits the same allelic combination as its parents pericentric inversion that involves the centromere polyploid individual with an incorrect number of chromosome sets recombination frequency average number of crossovers between two alleles; observed as the number of nonparental types in a population of progeny translocation process by which one segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome