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Klinefelter Syndrome. This young man exhibits many characteristics of Klinefelter syndrome: small testes, some development of the breasts, sparse body hair, and long limbs. This syndrome results from the presence of two or more X chromosomes with one Y chromosome (genotypes XXY or XXXY, for example). (Courtesy Nancy S. Wexler, PhD, Columbia University. Picked up from Patton KT, Thibodeau GA: Anatomy & physiology, ed 9, St Louis, 2016, Mosby.)
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Sex Chromosome Aneuploidy (cont’d) Question 3
A female has one X chromosome. Which diagnosis will the nurse observe documented on the chart?
Trisomy X syndrome
Klinefelter syndrome
Fragile X syndrome
Turner syndrome
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Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.
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Abnormalities of Chromosomal Structure
Effects may or may not have serious consequences.
Chromosome breakage
If a chromosome break occurs, then the break is usually repaired with no damage.
Breaks can stay or can heal in a way that alters the structure of the chromosome.
Can occur spontaneously.
Agents of chromosome breakage include Ionizing radiation, chemicals, and viruses.
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Abnormalities of Chromosomal Structure (cont’d)
Deletions
Chromosome breakage or loss of DNA
Example: Cri du chat syndrome or “cry of the cat”
Low birth weight, mentally challenged, and microcephaly
Duplications
Excess genetic material
Usually have less serious consequences
Inversion
Chromosomal rearrangement in which a chromosome segment is inverted: ABCDEFG becomes ABEDCFG
Usually affects offspring
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Abnormalities of Chromosomal Structure (cont’d)
Infant with cri du chat (5p deletion) syndrome
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-Occurs as a result of deletion of part of short arm portion of chromosome 5. Although one copy of chromosome is normal, serious consequences can still occur with deletions.
-Name derived from distinctive cry of newborn with this condition,
-Other symptoms include severe mental retardation, microcephaly, heart defects, and typical facial appearance seen in figure above.
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Abnormalities of Chromosomal Structure (cont’d)
Fragile sites (cont’d)
Fragile X syndrome
Site is on the long arm of the X chromosome; has an elevated number of repeated DNA sequences.
Is associated with being mentally challenged; is second in occurrence to Down syndrome.
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-Caused by an elevated number of repeated DNA sequences (more than 200) in the first exon of the fragile X gene. DNA replication becomes unstable, more than 20 genetic diseases are linked to this mechanism.
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Elements of Formal Genetics
Genetic inheritance
Mechanisms by which an individual’s set of paired chromosomes produces traits.
Explains the patterns of inheritance for traits and diseases that appear in families.
Mendelian traits
Are inherited traits primarily attributed to single genes.
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Elements of Formal Genetics (cont’d)
Locus: Is the location occupied by a gene on a chromosome.
Allele: Is one of several different forms of a gene at a locus.
One member of a gene from the mother; one member of a gene from the father
Homozygous: When genes are identical
Heterozygous: When genes are different
Polymorphism or polymorphic
Is a locus that has two or more alleles that occur with appreciable frequency.
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The way chromosomes are paired can produce specific traits.
Elements of Formal Genetics (cont’d)
Genotype: Is the composition of genes at a given locus.
Phenotype
Is the outward appearance of an individual.
Results from genotype and the environment.
Example: Infant with phenylketonuria (PKU) has the PKU genotype.
If left untreated, the infant will have cognitive impairments, which is the PKU phenotype.
If treated, the infant will still have the PKU genotype but can have a normal phenotype.
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-An individual’s genotype is his or her genetic makeup, and the phenotype reflects the interaction of the genotype and environment
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Elements of Formal Genetics (cont’d)
Dominance and recessiveness
If two alleles are found together, then the allele that is observable is dominant and the one whose effects are hidden is recessive.
In genetics, the dominant allele = a capital letter, and the recessive allele = a lowercase letter.
Alleles are either heterozygote or homozygote.
Alleles can be co-dominant; that is, both alleles are expressed.
Carrier
Has a disease allele but is phenotypically normal.
Can pass disease to offspring.
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-At a heterozygous locus, a dominant gene’s effects mask those of a recessive gene. The recessive gene is expressed only when it is present in 2 copies.
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Transmission of Genetic Diseases
Mode of inheritance: Is the inherited patterns through the generations of a family.
Mendel’s two laws
Principle of segregation
Homologous genes separate from one another.
Each cell carries only one of the homologous genes.
Principle of independent assortment
Hereditary transmission of one gene has no effect on the transmission of another.
Chromosome theory of inheritance
Chromosomes follow Mendel’s two laws.
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Transmission of Genetic Diseases (cont’d)
Four major types of genetic diseases
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
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Genetic diseases caused by a single gene usually follows autosomal dominant, autosomal recessive, or X-linked recessive modes of inheritance
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Transmission of Genetic Diseases (cont’d)
Pedigree
Is the tool used to study specific genetic disorders within families.
Begins with the proband.
Propositus (male) or proposita (female)
Usually the first person in the family diagnosed or seen in a clinic
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-Pedigree charts are important tools in the analysis of modes of inheritance
-Propositus/proposita is the individual who usually is the first diagnosed or seen in clinic with the disease
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Autosomal Dominant Inheritance
Diseases are rare.
Occurs in fewer than 1 of 500 individuals.
The union of a normal parent with an affected heterozygous parent usually produces the affected offspring.
An affected parent can pass either a disease gene or a normal gene to his or her children; each event has a probability of 0.5; on average, half will be heterozygous and will express the disease and half will be normal.
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– No generational skipping occurs.
-Condition is expressed equally in males and females, and males and females are equally likely to pass the gene to his or her offspring.
-Recurrence risk: probability that family member will have genetic disease
-When one parent is affected by an autosomal dominant disease and the other is normal, the occurrence and recurrence risks for each child are one half.
-Each birth is an independent event.
-New mutation: Is when no history of an autosomal dominant condition is present, but the child develops the mutation.
-Offspring of affected child will have 50% chance of genetic disease (recurrence risk)
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Autosomal Dominant Inheritance (cont’d)
Characteristics of autosomal dominant inheritance
Condition is expressed equally in males and females, and males and females are equally likely to pass the gene to his or her offspring.
Approximately one-half of children of an affected heterozygous parent will express the condition (all or none of the children may have the condition).
No generational skipping occurs.
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Autosomal Dominant Inheritance (cont’d)
Recurrence risk (cont’d)
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Review figure 4-20 on page 153
Punnett Square and Autosomal Dominant Traits. A, Punnett square for the mating of two individuals with an autosomal dominant gene. Here both parents are affected by the trait. B, Punnett square for the mating of a normal individual with a carrier for an autosomal dominant gene.
