Inheritance PDF

1/16/24, 10:09 PM Realizeit for Student Inheritance The nucleus within the cell is the controlling factor in all cellular activities because it contains chromosomes, long continuous strands of deoxyribonucleic acid (DNA) that carry genetic information. DNA is the hereditary material found in human...

1/16/24, 10:09 PM Realizeit for Student Inheritance The nucleus within the cell is the controlling factor in all cellular activities because it contains chromosomes, long continuous strands of deoxyribonucleic acid (DNA) that carry genetic information. DNA is the hereditary material found in humans which can replicate itself. Each chromosome is made up of genes. Genes are individual units of heredity of all traits and are organized into long segments of DNA that occupy a specific location on a chromosome and determine a particular characteristic in an organism. DNA stores genetic information and encodes the instructions for synthesizing specific proteins needed to maintain life. DNA is double stranded and takes the form of a double helix. The side pieces of the double helix are made up of a sugar, deoxyribose, and a phosphate, occurring in alternating groups. The cross connections or rungs of the ladder are attached to the sides and are made up of four nitrogenous bases: adenine, cytosine, thymine, and guanine. The sequence of the base pairs as they form each rung of the ladder is referred to as the genetic code (Fig. 10.10) (GHR, 2019b). FIGURE 10.10. DNA is made up of four chemical bases. Tightly coiled strands of DNA are packaged in units called chromosomes, housed in the cell’s nucleus. Working subunits of DNA are known as genes. (From the National Institutes of Health and National Cancer Institute. [1995]. Understanding gene testing [NIH Pub. No. 96–3905]. U.S. Department of Human Services.) https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 1/10 1/16/24, 10:09 PM Realizeit for Student Each gene has a segment of DNA with a specific set of instructions for making proteins needed by body cells for proper functioning. Genes control the types of proteins made and the rate at which they are produced (Norton et al., 2019). Any change in gene structure or location leads to a mutation, which may alter the type and amount of protein produced (Fig. 10.11). Genes never act in isolation; they always interact with other genes and the environment. They are arranged in a specific linear formation along a chromosome. The genotype, the specific genetic makeup of an individual, usually in the form of DNA, is the internally coded inheritable information. It refers to the particular allele, which is one of two or more alternative versions of gene at a given position or locus on a chromosome that imparts the same characteristic of that gene. For instance, each human has a gene that controls height, but there are variations of these genes, which https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 2/10 1/16/24, 10:09 PM Realizeit for Student are alleles, in accordance with the specific height for which the gene codes. A gene that controls eye color may have an allele that can produce blue eyes or an allele that produces brown eyes. The genotype, together with environmental variation that influences the individual, determines the phenotype, or the observed, outward characteristics of an individual. A human inherits two genes, one from each parent. Therefore, one allele comes from the mother and one from the father. These alleles may be the same for the characteristic (homozygous) or different (heterozygous). For example, WW stands for homozygous dominant; ww stands for homozygous recessive. Heterozygous would be indicated as Ww. If the two alleles differ, such as Ww, the dominant one will usually be expressed in the phenotype of the individual. FIGURE 10.11 When a gene contains a mutation, the protein encoded by that gene will be abnormal. Some protein changes are insignificant, while others are disabling. (From the National Institutes of Health and National Cancer Institute. [1995]. Understanding gene testing [NIH Pub. No. 96–3905]. Washington, DC: U.S. Department of Human Services.) Human beings typically have 46 chromosomes. This includes 22 pairs of nonsex chromosomes or autosomes and one pair of sex chromosomes (two X chromosomes in females, and an X chromosome and a Y chromosome in males). Offspring receive one chromosome of each of the 23 pairs from each parent. Patterns of Inheritance for Genetic Disorders Patterns of inheritance demonstrate how genetic abnormalities can be passed on to offspring. Although diagnosis of a genetic disorder is usually based on clinical signs and https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 3/10 1/16/24, 10:09 PM Realizeit for Student symptoms or on laboratory confirmation of an altered gene associated with the disorder, accurate diagnosis can be aided by the recognition of the pattern of inheritance within a family. In addition, nurses must understand the patterns of inheritance so they can teach and counsel families about the risks of genetic disorders occurring in future pregnancies. Some genetic disorders occur in multiple family members, while others may occur in only a single family member. A genetic disorder is caused by completely or partially altered genetic material, whereas a familial disorder is more common in relatives of the affected individual but may be caused by environmental influences and not genetic alterations. Mendelian or Monogenic Laws of Inheritance Principles of inheritance of single-gene disorders are the same principles that govern the inheritance of other traits, such as eye and hair color. These are known as Mendel’s laws of inheritance, named for Gregory Mendel, an Austrian naturalist who conducted genetic research. These patterns occur because a single gene is defective and the disorders that result are referred to as monogenic or, sometimes, Mendelian disorders. If the defect occurs on the autosome, the genetic disorder is termed autosomal; if the defect is on the X chromosome, the genetic disorder is termed X-linked. The defect also can be classified as dominant or recessive. Monogenic disorders include autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive patterns. AUTOSOMAL DOMINANT INHERITANCE DISORDERS Autosomal dominant inherited disorders occur when a single gene in the heterozygous state is capable of producing the phenotype. In other words, the abnormal or mutant gene overshadows the normal gene and the person will demonstrate signs and symptoms of the disorder. The affected person generally has one affected parent. However, there are varying degrees of presentation among individuals in a family. For example, a parent with a mild form of the disorder could have a child with a more severe form (termed variable expression). In some autosomal dominant disorders there may be no history of an affected family member. This can be due to the child representing a new mutation or the result of incomplete or reduced penetrance, which means that a person with the genetic mutation does not develop phenotypic features of the disorder. Incomplete or reduced penetrance may result from a combination of genetic, environmental, and lifestyle factors, age, and gender. Offspring of an affected parent will have a 50% chance of inheriting two normal genes (disorder free) and a 50% chance of inheriting one normal and one abnormal gene (and, thus, the disorder). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 4/10 1/16/24, 10:09 PM Realizeit for Student AUTOSOMAL RECESSIVE INHERITANCE DISORDERS Autosomal recessive inherited disorders occur when two copies of the mutant or abnormal gene in the homozygous state are necessary to produce the phenotype. In other words, two abnormal genes are needed for the individual to demonstrate signs and symptoms of the disorder. Both parents of the affected person must be heterozygous carriers of the gene (clinically normal but carriers of the gene). Offspring of two carriers of the abnormal gene have a 25% chance of inheriting two normal genes; a 50% chance of inheriting one normal gene and one abnormal gene (carrier); and a 25% chance of inheriting two abnormal genes (and, thus, the disorder) (Fig. 10.14) (GHR, 2019c). Affected people are usually present in only one generation of the family. Females and males are equally affected and a male can pass the disorder on to his son. The chance that any two parents will both be carriers of the mutant gene is increased if the couple has consanguinity (relationship by blood or common ancestry) (GHR, 2019c). Common types of genetic disorders that follow the autosomal recessive inheritance pattern include cystic fibrosis (a genetic disorder involving generalized dysfunction of the exocrine glands), phenylketonuria (a disorder involving a deficiency in a liver enzyme that leads to the inability to process the essential amino acid phenylalanine), Tay–Sachs disease (a disorder due to insufficient activity of the enzyme hexosaminidase, which is necessary for the breakdown of certain fatty substances in the brain and nerve cells), and sickle cell disease (a genetic disorder in which the red blood cells carry an ineffective type of hemoglobin instead of the normal adult hemoglobin). FIGURE 10.14 Autosomal recessive inheritance. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 5/10 1/16/24, 10:09 PM Realizeit for Student X-LINKED INHERITANCE DISORDERS X-linked inherited disorders are those associated with altered genes present on the X chromosome. They differ from autosomal disorders. If a male inherits an X-linked altered gene, he will express the condition. This is because a male has only one X chromosome, therefore all the genes on his X chromosome will be expressed (the Y chromosome carries no normal allele to compensate for the altered gene). Because females inherit two X chromosomes, they can be either heterozygous or homozygous for any allele. Therefore, X-linked disorders in females are expressed similarly to autosomal disorders. X-LINKED RECESSIVE INHERITANCE Most X-linked disorders demonstrate a recessive pattern of inheritance (GHR, 2019c). There are more affected males than females because all the genes on a man’s X chromosome will be expressed since a male has only one X chromosome (Scott & Lee, 2020). On the other hand, a female will usually need two abnormal X chromosomes to exhibit the disease, and one normal and one abnormal X chromosome to be a carrier of the disease. There is no male-to-male transmission (since no X chromosome from the male is transmitted to male offspring), but any man who is affected with an X-linked recessive disorder will have carrier daughters. If a woman is a carrier, there is a 25% chance she will have an affected son, a 25% chance that her daughter will be a carrier, a 25% chance that she will have an unaffected son, and a 25% chance her daughter https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 6/10 1/16/24, 10:09 PM Realizeit for Student will be a noncarrier (Fig. 10.15) (Scott & Lee, 2020). Common types of genetic disorders that follow X-linked recessive inheritance patterns include hemophilia, color blindness, and Duchenne muscular dystrophy (GHR, 2019c). FIGURE 10.15 X-linked recessive inheritance X-LINKED DOMINANT INHERITANCE X-linked dominant inheritance occurs when a male has an abnormal X chromosome or a female has one abnormal X chromosome. All of the daughters and none of the sons of an affected male will inherit the condition, while both male and female offspring of an affected woman have a 50% chance of inheriting the condition (GHR, 2019c). Males are more severely affected than females. Many X-linked dominant disorders have lethal results in males (Zirn & Mehnert, 2019). In females, even though the gene is dominant, having a second normal X gene offsets the effects of the dominant gene to some extent resulting in decreasing severity of the disorder. X-linked dominant disorders are rare; examples include hypophosphatemic (vitamin D–resistant) rickets and fragile X syndrome. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 7/10 1/16/24, 10:09 PM Realizeit for Student Multifactorial Inheritance Disorders Many of the common congenital malformations, such as cleft lip, cleft palate, spina bifida, pyloric stenosis, clubfoot, congenital hip dysplasia, and cardiac defects, are attributed to multifactorial inheritance (Sharma et al., 2019). These conditions are thought to be caused by multiple gene and environmental factors. That is, a combination of genes from both parents, along with unknown environmental factors, produces the trait or condition. Chromosomal Abnormalities In some cases of genetic disorders, the abnormality occurs due to problems with the chromosomes. Chromosomal abnormalities do not follow straightforward patterns of inheritance. Although some chromosomal disorders can be inherited, most others occur due to random events during the formation of reproductive cells or in early fetal development. Most chromosomal abnormalities occur due to an error in the egg or sperm. Therefore, the abnormality is present in every cell of the body. Some abnormalities can happen after fertilization, during mitotic cell division, and result in mosaicism. Mosaicism or the mosaic form is when the chromosomal abnormalities do not show up in every cell; only some cells or tissues carry the abnormality. In mosaic forms of the disorder the symptoms are usually less severe than if all the cells were abnormal. Chromosomal abnormalities occur in about one in 150 live-born infants (March of Dimes, 2019a). Congenital anomalies and intellectual disability are often associated with chromosomal abnormalities (Pyeritz et al., 2019). These abnormalities occur on autosomal or nonsex chromosomes as well as sex chromosomes and can result from abnormalities of either chromosome number or chromosome structure. As mentioned, a karyotype is a pictorial analysis of chromosomes. It depicts a systematic arrangement of chromosomes of a single cell by pairs. Karyotyping is often used in prenatal testing to diagnose or predict genetic diseases. Abnormalities of Chromosome Number Chromosomal abnormalities of number often result due to nondisjunction (failure of separation of the chromosome pair during cell division, meiosis, or mitosis). Few chromosomal numerical abnormalities are compatible with full-term development and most result in spontaneous abortion (Bacino, 2019). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 8/10 1/16/24, 10:09 PM Realizeit for Student There are some numerical abnormalities that do support development to term because the chromosome on which the abnormality is present carries relatively few genes (such as chromosome 13, 18, 21, or X). Two common abnormalities of chromosome number are monosomies and trisomies. In monosomies, there is only one copy of a particular chromosome instead of the usual pair (an entire single chromosome is missing). In these cases, all fetuses spontaneously abort in early pregnancy. Survival is seen only in mosaic forms of these disorders. In trisomies, there are three of a particular chromosome instead of the usual two (an entire single chromosome is added). The most common trisomies include trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. Abnormalities of Chromosome Structure Abnormalities of chromosome structure usually occur when there is a breakage and loss of a portion of one or more chromosomes, and during the repair process the broken ends are rejoined incorrectly. Structural abnormalities usually lead to having too much or too little genetic material. Altered chromosome structure can take on several forms. Deletions occur when a portion of the chromosome is missing or deleted, resulting in a loss of that portion of the chromosome. Duplications are seen when a portion of the chromosome is duplicated and an extra chromosomal segment is present. Clinical findings vary depending on how much chromosomal material is involved. Inversions occur when a portion of the chromosome breaks off at two points and is turned upside down and reattached; therefore, the genetic material is inverted. With inversion, there is no loss or gain of chromosomal material and carriers are phenotypically normal, but they do have an increased risk for miscarriage and having chromosomally abnormal offspring (GHR, 2019c). Ring chromosomes are seen when a portion of a chromosome has broken off in two places and formed a circle or ring. The most clinically significant structural abnormality is a translocation. This occurs when a portion of one chromosome is transferred to another chromosome and an abnormal rearrangement is present. Structural abnormalities can be balanced or unbalanced. Balanced abnormalities involve the rearrangement of genetic material with neither an overall gain nor loss. Individuals who inherit a balanced structural abnormality are usually phenotypically normal but are at a higher risk for miscarriages and having chromosomally abnormal offspring. Examples of structural rearrangements that can be balanced include inversions, translocation, and ring chromosomes. Unbalanced structural abnormalities are similar to numerical abnormalities because genetic material is either gained or lost. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 9/10 1/16/24, 10:09 PM Realizeit for Student Unbalanced structural abnormalities can encompass several genes and result in severe clinical consequences. Sex Chromosome Abnormalities Chromosomal abnormalities can also involve sex chromosomes. These cases are usually less severe in their clinical effects than autosomal chromosomal abnormalities. Sex chromosome abnormalities are gender specific and involve a missing or extra sex chromosome. They affect sexual development and may cause infertility, growth abnormalities, and possibly behavioral and learning problems (Bacino, 2019). However, many affected people lead essentially normal lives. Examples are Turner syndrome in females and Klinefelter syndrome in males. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zTYaQRcVeGjlcsXn1BnhV1BdrBMb3lqiFIhL1oNdUK7j0NCYT… 10/10