Sex Chromosome Abnormalities

 Turner’s syndrome: 1/3000 females

 A single X chromosome

 Pattern of physical traits

 Klinefelter syndrome: 1/200 males

 XXX

 Sterile, feminine traits Mutations

 A change in structure/arrangement

 Produces a new phenotype

 Sperm more likely than ova

 May be harmful or beneficial Mutations

 Errors in chromosome division during meiosis

 Too many or too few chromosomes

 Most spontaneously aborted

 Down Syndrome: Trisomy 21

 Physical deformities

 Mental retardation

 Related to age of parents Many inherited disorders in humans are controlled by a single gene

Normal Normal PARENTS Dd Dd

D D  Most such disorders Eggs Sperm DD Normal are caused by d d autosomal recessive Dd Dd OFFSPRING Normal Normal alleles (carrier) (carrier)

 dd Examples: Deaf cystic fibrosis, sickle-cell disease Figure 9.9A Table 9.9 Chromosome Abnormalities

 Errors in chromosome division during meiosis

 Too many or too few chromosomes

 Most spontaneously aborted

 Down Syndrome: Trisomy 21

 Physical deformities

 Mental retardation

 Related to age of parents Examples of autosomal dominant disorders

 ‰ Huntington’s disease

 ‰ Achondroplastic dwarfism

 ‰ Myotonic dystrophy

 ‰ Piebald spotting Huntingtons Chorea

 Degenerative disease of the nervous system

 Late-acting dominant allele

 Irreversible and lethal once

 deterioration of nervous system begins

 The phenotypic affects do not appear until 35-40 years of age (by which time most people have transmitted the gene to their children) Karyotyping

 A karyotype is a display of the chromosomes of a single cell.  The chromosomes are spread out so that they all can be seen.  They are stained with dyes to accentuate differences between the chromosomes, which is helpful in telling them apart. Karyotyping

 This is the karyotype, from a normal person. CHROMOSOMAL DELETIONS

 Monosomy 23 X - (X0) - Turner's Syndrome

 Partial Deletion of Upper Arm of Chromosome 5 - Cry of the Cat (Cri du Chat) CHROMOSOMAL ADDITIONS

 Trisomy 13 - Patau's Syndrome

 Trisomy 18 - Edward's Syndrome

 Trisomy 21 - Down Syndrome

 Trisomy 23 X - (XXY) Klinefelter's Syndrome

 Trisomy 23 Y - XYY Syndrome Single-Gene Disorders

 Some disorders result when a mutation causes the product of a single gene to be altered or missing.  An example of this kind of disorder is sickle- cell anemia.

 Other single-gene disorders are Cystic Fibrosis, Muscular Dystrophy, Huntington’s disorder and Marfan Syndrome Abnormal Chromosomes

 Nondisjunction is the failure of Homologous chromosomes to separate during Meiosis I or the failure of sister chromatids to separate during Meiosis II. Abnormal Chromosomes

 Extra or missing chromosomes can interfere with normal development or result in recognizable syndromes Disorder Descriptions

 Albinism - The word "albinism" refers to a group of inherited conditions. People with albinism have little or no pigment in their eyes, skin, or hair. They have inherited genes that do not make the usual amounts of a pigment called melanin.

 Tourette Syndrome is an inherited, neurological disorder characterized by repeated and involuntary body movements (tics) and uncontrollable vocal sounds. In a minority of cases, the vocalizations can include socially inappropriate words and phrases -- called coprolalia. These outbursts are neither intentional nor purposeful. Involuntary symptoms can include eye blinking, repeated throat clearing or sniffing, arm thrusting, kicking movements, shoulder shrugging or jumping.

 The Marfan syndrome is a heritable condition that affects the connective tissue. The primary purpose of connective tissue is to hold the body together and provide a framework for growth and development. In the Marfan syndrome, the connective tissue is defective and does not act as it should. Because connective tissue is found throughout the body, the Marfan syndrome can affect many body systems, including the skeleton, eyes, heart and blood vessels, nervous system, skin and lungs. Disorders Continued

 Turner syndrome (TS) is a chromosomal condition that describes girls and women with common features that are caused by complete or partial absence of the second sex chromosome. TS occurs when one of the two X chromosomes normally found in females is missing or contains certain structural defects. The syndrome is named after Dr. Henry Turner, who was among the first to describe its features in the 1930s. TS occurs in approximately 1 in 2,000 live female births.  The neurofibromatoses (NF) are a set of genetic disorders which cause tumors to grow along various types of nerves and, in addition, can affect the development of non-nervous tissues such as bones and skin. NF causes tumors to grow anywhere on or in the body. It also leads to developmental abnormalities. For example, individuals with NF have a higher incidence of learning disabilities.  Tay-Sachs disease is a fatal genetic disorder in which harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain. Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. Disorders continued

 One of nine types of muscular dystrophy, a group of genetic, degenerative diseases primarily affecting voluntary muscles.  Cause — An absence of dystrophin, a protein that helps keep muscle cells intact.  Onset — Early childhood - about 2 to 6 years. Symptoms — Generalized weakness and muscle wasting first affecting the musclesof the hips, pelvic area, thighs and shoulders. Calves are often enlarged. Progression — DMD eventually affects all voluntary muscles, and the heart and breathing muscles. Survival is rare beyond the early 30s Disorders continued

 SICKLE CELL ANEMIA (SCA) is the most common inherited blood disorder in the United States, affecting about 72,000 Americans or 1 in 500 African Americans. SCA is characterized by episodes of pain, chronic hemolytic anemia and severe infections, usually beginning in early childhood  Hutchinson-Gilford Progeria Syndrome is an extremely rare genetic disease that accelerates the aging process to about seven times the normal rate. Because of this accelerated aging, a child of ten years will have similar respiratory, cardiovascular, and arthritic conditions that a 70- year-old would have. Disorders Continued

 Fragile X syndrome, called Martin-Bell syndrome, is a genetic disorder and is the most common form of inherited mental retardation. It is a sex-linked genetic abnormality in which a mother is a carrier, transmitting the disorder to her sons. It affects approximately 1 in every 1,000 to 2,000 male individuals, and the female carrier frequency may be substantially higher. Males afflicted with this syndrome typically have a moderate to severe form of intellectual handicap. Females may also be affected but generally have a mild form of impairment. Approximately 15% to 20% of those with Fragile X Syndrome exhibit autistic- type behaviors, such as poor eye contact, hand-flapping or odd gesture movements, hand-biting, and poor sensory skills. Behavior problems and speech/language delay are common features of Fragile X Syndrome.  People with Fragile X syndrome also have a number of recognizable physical features, including a high arched palate, strabismus (lazy eye), large ears, long face, large testicles in males, poor muscle tone, flat feet, and sometimes mild, heart valve abnormalities. Although most individuals with Fragile X syndrome have a characteristic 'look' (long face and large ears), there are some who do not have typical features.

 Klinefelter’s Syndrome Multifactorial Disorders

 Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes.  The complicated bases of these diseases make them difficult to study and to treat.  Heart disorder, diabetes and cancer are examples of this type of disorder.  Other examples include: Lupus and Tourette’s Syndrome Genetic testing can detect disease- causing alleles

 Genetic testing can be of value to those at risk of developing a genetic disorder or of passing it on to offspring Figure 9.15B

 Dr. David Satcher, former U.S. surgeon general, pioneered screening for sickle-cell disease

Figure 9.15A