Unit #9: Genetic and Developmental Disorders ( Flashcards
Define: Chromosome
A linear thread of nuclear DNA that becomes visible under the microscope during cell mitosis.
Define: Genes
A unit of heredity consisting of a segment of DNA nucleotides that encodes a messenger RNA capable of being translated into a protein.
Define: Alleles
One of two or more alternative forms of a gene located at the same site on the homologous chromosomes.
Define: Heterzygous
Having two different alleles for a specific gene product.
Define: Homozygous
Having two identical alleles for a specific gene product.
Define: Mutation/abberation
A heritable change in the nucleotide sequence of a chromosome; it is passed on to daughter cells when the cells divide.
Define: Genotype
The genetic constitution of an individual; often described by listing the allele types at a certain gene locus.
Define: Phenotype
The physical, biochemical, and biological composition of an individual; expressed as a recognizable trait.
Define: Congenital defect
A general term meaning a defect in form or function that is present at birth.
Define: Teratogen
An agent or factor that causes damage or physical defects in a developing embryo.
Describe: Chromosomal disorders
- Generally occur due to an abnormal number of chromosomes or alterations in the structure of one or more chromosomes.
- Errors in separation of chromosome during meiosis may result in abnormal numbers of chromosomes
- Can be tested for during pregnancy
Describe: Autosomal dominant disorders
- Dominant inheritance means an abnormal gene from one parent can cause disease. This happens even when the matching gene from the other parent is normal. The abnormal gene dominates.
- This disease can also occur as a new condition in a child when neither parent has the abnormal gene.
- A parent with an autosomal dominant condition has a 50% chance of having a child with the condition. This is true for each pregnancy.
Describe: Autosomal recessive disorders
- An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop.
- Recessive inheritance means both genes in a pair must be abnormal to cause disease. People with only one defective gene in the pair are called carriers. These people are most often not affected with the condition. However, they can pass the abnormal gene to their children.
Describe: Sex-linked (X-linked) disorders
- Sex-linked diseases are passed down through families through one of the X or Y chromosomes.
- Dominant inheritance occurs when an abnormal gene from one parent causes disease even though the matching gene from the other parent is normal. The abnormal gene dominates.
- But in recessive inheritance, both matching genes must be abnormal to cause disease. If only one gene in the pair is abnormal, the disease does not occur or it is mild. Someone who has one abnormal gene (but no symptoms) is called a carrier. Carriers can pass abnormal genes to their children.
- The term “sex-linked recessive” most often refers to X-linked recessive.
- X-linked recessive diseases most often occur in males. Males have only one X chromosome. A single recessive gene on that X chromosome will cause the disease.
- The Y chromosome is the other half of the XY gene pair in the male. However, the Y chromosome doesn’t contain most of the genes of the X chromosome. Because of that, it doesn’t protect the male. Diseases such as hemophilia and Duchenne muscular dystrophy occur from a recessive gene on the X chromosome.
- females can get an X-linked recessive disorder, but this is very rare. An abnormal gene on the X chromosome from each parent would be required, since a female has two X chromosomes.
Describe: Multifactorial (Polygenic) disorders
- Polygenic traits develop in response to more than one gene.
- Multifactorial disorders are very common and result from the interaction of multiple genes and environmental influences. Disorders such as high blood pressure, cancer, and diabetes are multifactorial.
What is the pathogenesis of Down Syndrome?
• An extra chromosome 21 from meiotic non-disjunction or failure of the chromosome pairs to separate during gamete formation is present in about 95% of individuals with DS. Population-based studies show that over 90% of non-disjunction errors leading to trisomy 21 occur in the oocyte and predominantly in maternal meiosis I.
What is the clinical manifestation of Down Syndrome?
- Decreased or poor muscle tone
- Short neck, with excess skin at the back of the neck
- Flattened facial profile and nose
- Small head, ears, and mouth
- Upward slanting eyes, often with a skin fold that comes out from the upper eyelid and covers the inner corner of the eye
- White spots on the colored part of the eye (called Brushfield spots)
- Wide, short hands with short fingers
- A single, deep, crease across the palm of the hand
- A deep groove between the first and second toes
What is the pathogenesis of Turner Syndrome?
- Turner syndrome is associated with the presence of only one normal X chromosome and no Y chromosome.
- The absence of the Y chromosome results in a female phenotype; the overaires fail to develop or fail prematurely.
- In some cases the second X chromosome is not entirely missing but is structurally abnormal.
- In most cases the missing or damaged X chromosomes is of paternal origin
What is the clinical manifestation of Turner Syndrome?
- Short stature
- Webbing of the neck
- A wide chest
- Lymphedema of the hands and feet at birth
- Congenital heart defects
- Failure to develop secondary sexual characteristics
What is the pathogenesis of Klinefelter Syndrome?
- Individuals with this disorder usually have an extra X chromosome (an XXY genotype).
- There have also been cases of more than one extra X chromosome (XXXY and XXXXY).
- The presence of the Y chromosomes determines the sex of the individuals to be male, however, if there is an extra X chromosome it results in abnormal sexual development and feminization
- Rarely diagnosed before puberty
What is the clinical manifestation of Klinefelter Syndrome?
- Lack of testosterone (testicular atrophy and infertility)
- Tall stature with long arms and legs
- Feminine hair distribution
- Gynecosmastia (breast enlargement)
- High-pitched voice
- Impaired intelligence
What is the pathogenesis of Cystic Fibrosis?
• Cystic fibrosis is caused by defects in the cystic fibrosis gene, which codes for a protein transmembrane conductance regulator (CFTR) that functions as a chloride channel and is regulated by cyclic adenosine monophosphate (cAMP). Mutations in the CFTR gene result in abnormalities of cAMP-regulated chloride transport across epithelial cells on mucosal surfaces.
Clinical Manifestation
What is the clinical manifestation of Cystic Fibrosis?
- Severe chronic lung disease
- Exocrine pancreatic insufficiency
- Nasal polyposis
- Pansinusitis
- Rectal prolapse
- Chronic diarrhea
- Cholelithiasis
- Cirrhosis or other forms of hepatic dysfunction
What is the pathogenesis of Huntington Disease?
- Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex.
- The most striking neuropathology in HD occurs within the neostriatum, in which gross atrophy of the caudate nucleus and putamen is accompanied by selective neuronal loss and astrogliosis. Marked neuronal loss also is seen in deep layers of the cerebral cortex. Other regions, including the globus pallidus, thalamus, subthalamic nucleus, substantia nigra, and cerebellum, show varying degrees of atrophy depending on the pathologic grade.
- The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin