13.1 Counseling for chromosomal disorders• Genetic counseling – potential parents are advised on their risk of inherited disorders.• Counselor helps couple understand the mode of inheritance, medical consequences of disorder and decisions they might wish to make.• Karyotyping – visual display of chromosomes arranged by size, shape and banding pattern • Can be from white blood cells or fetal cells by amniocentesis or chorionic villus sampling
• Chromosomal mutations Karyotype reveals changes in chromosome number and differences in structure. In humans only a few variations in number are typically seen. • Down syndrome, Turner syndrome, Klinefelter syndrome Changes in chromosome structure more common • Due to breakage and failure to reunite properly • Results in deletion, duplication, translocation or inversion
• Deletion When a single break causes a chromosome to lose an end or 2 breaks result in the loss of an internal segment Williams syndrome – chromosome 17 loses a tiny end piece. Cri du chat – chromosome 5 loses an end piece.
• Duplication Chromosome segment repeated Individual has more than 2 alleles for certain traits. Inv dup 15 syndrome – inverted duplication of chromosome 15 • Inversion – segment joins in direction opposite from normal.
• Translocation Exchange of chromosome segments between nonhomologous chromosomes A person with both the involved chromosomes has a normal amount of genetic material and is healthy unless the exchange disrupts a gene. 5% of Down syndrome cases caused by a translocation in previous generation between chromosome 21 and 14 • Not related to parental age but is inherited
• Alagille syndrome Translocation between chromosome 2 and 20 Normal amount of genetic material but distinctive face, some abnormalities and severe itching Translocation disrupted allele on chromosome 20 Father did not realize he had the syndrome until he had this child.
• Inversion Segment of a chromosome is turned 180° Reverse sequence of alleles can lead to altered gene activity if it disrupts control of gene expression. Usually do not cause problems During meiosis, crossing-over can lead to recombinant chromosomes. • Alignment only possible when inverted chromosome forms a loop
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13.2 Counseling for Genetic Disorders• Even if no chromosomal abnormality is likely, amniocentesis might still be done to perform biochemical tests for over 400 different disorders caused by specific genes.• Counselor needs to know medical history of family to construct a pedigree• Determines what tests are warranted
• Pedigree Chart of a family’s history with regard to a particular genetic trait • Males are squares • Females are circles • Shading represents individuals expressing disorder. • Horizontal line between circle and square is a union. • Vertical line down represents children of that union. Counselor may already know pattern of inheritance and then can predict chance that child born to a couple would have the abnormal phenotype.
• Pedigrees for autosomal disorders Autosomal recessive disorder • Child can be affected when neither parent is affected • Heterozygous parents are carriers • Parents can be tested before having children
Autosomal dominant disorder •Child can be unaffected even when parents are heterozygous and therefore affected. •When both parents are unaffected, none of their children will have the condition. No dominant gene to pass on
• Pedigree for sex-linked disorder X-linked recessive disorder • Sons inherit trait from mother – son’s X comes from mother. • More males than females have disorder – allele on X is always expressed in males. • Females who have the condition inherited the mutant allele from both their mother and their father. • Conditions appear to pass from grandfather to grandson.
X-linked dominant • Only a few traits • Daughters of affected males have the condition. • Affected females can pass condition to daughters and sons. Depends on which X inherited from a carrier mother if father is normal Y chromosome • Only a few disorders • Present only in males and are passed to all sons but not daughters
X-linked recessive disorders • Color blindness About 8% of Caucasian men have red-green color blindness. • Duchenne muscular dystrophy Absence of protein dystrophin causes wasting away of muscles. Therapy – immature muscle cells injected into muscles
• Testing for genetic disorders Testing for a protein • Some disorders caused by a missing enzyme Test for quantity of enzyme produced Testing the DNA • Genetic marker – relies on an abnormality in the DNA sequence due to presence of abnormal allele. Fragments from restriction digest will differ from a normal person’s results.
• Genetic profiling Individual’s complete genotype DNA sample applied to DNA chip DNA chip contains probes – single-stranded DNA that binds to complementary DNA from patient Binding shows patient has particular mutated genes
Testing the embryo and egg • Testing egg – meiosis results in single egg and 2 polar bodies. • Polar bodies can be used in genetic testing. • If a woman is a heterozygote, when the polar body has the defective allele, the egg must be normal.
13.3 Gene Therapy• Insertion of genetic material into human cells for treatment of a disorder• 2 methods Ex vivo – outside the body In vivo – inside the body
• Ex vivo Treatment of SCIDS • Severe combined immunodeficiency • Lack enzyme involved in maturation of cells producing antibodies • Bone marrow are stem cells removed and infected with RNA retrovirus carrying gene for normal enzyme. • Cells are then retuned to patient. Treatment of familial hypercholesterolemia • High levels of cholesterol lead to early fatal heart attacks. • Small portion of liver is removed and infected with retrovirus containing normal cholesterol receptor. • Tissue is returned to patient.
• In vivo Cystic fibrosis treatment • Gene needed is sprayed into the nose or delivered to lower respiratory tract. • Use adenoviruses or liposomes to carry gene Poor coronary circulation treatment • Vascular endothelial growth factor can cause growth of new blood vessels. • Genes coding for growth factor can be injected alone, or within a virus, into the heart to stimulate branching of coronary arteries. Rheumatoid arthritis • Immune system destroys person’s own body. • Inject adenoviruses that contain anti-inflammatory genes into the affected joint