بسم الله الرحمن الرحيم
Genetic Diseases
Dr : Kawkab Adris Mahmood Lecturer / Microbiology College of Medicine Department of Anatomy
Genetic Disorder :
is a disease that is caused by an abnormality in an individuals DNA . Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes . Some genetic disorders are inherited from the parents while other genetic diseases are caused by mutation in preexisting gene or group of genes .Genetic material : In human the genetic material 46 chromosomes 44 autosomal chromosomes and 2 sex chromosomes (44 autosomal chromosomes plus 2 sex chromosomes (XX in females ) . And 44 autosomal chromosomes plus 2 sex chromosomes (XY in males ) Karyotype : The chromosome constitution of a cell or an individual . Chromosomes arranged in pairs according to their length and position of centromere at mitotic metaphase.
Chromosome: The structure by which hereditary information is transmitted from one generation to the next. Located in the nucleus, it is consists of tightly coiled thread of DNA with associated proteins and RNA. The genes are arranged in linear order along the DNA .
Gene : is acertain segment of DNA that contains the necessary code to make RNA or polypeptide ( proteins ) . Gene accomplish their function through replication and transcription and translation whereby proteins that function as determiners in the metabolism of the cell are synthesized Mutation : a change in the DNA at aparticular locus in an organism . The term is used loosely to include point mutations involving single gene change as well as chromosomal change .
Types of Genetic Disorders :
1- Single gene Disorder : These disorder result when a mutation causes the protein product of a single gene to be altered or missing . ( mutation in a single gene ) . Such as :Sickle cell anemia : is ahereditary disease caused by abnormal hemoglobine molecules lead to sickle shaped red cells, anemia, and blocked circulation .
Sickle cell anemia
2- X-Linked Disease : Are single gene disorders that reflect the presence of defective gene on the X-chromosome. This chromosome is present as two copies in females but only as one copy in males . X-Linked disease include red-green colourblindness and hemophilia . These diseases are much more common in males than females .Colourblindness : is the redused ability to distinguish between certain coloures . Its usually inherited and is more common in men than in women because two of the mutant allele are required for the disease to occur in females, while only one copy required in males . The gene for red-green colourblindness lies on the X-chromosome.
Diagnosis :
Test for colourblindness : which consists of aseries of pictures of colored spots, is the most often used to diagnose red-green color deficiencies . Afigure is embedded in the picture as anumber of spots in aslightly different color, and can be seen with normal color vision , but not with aparticular color defect .
Hemophilia :
Is a rare genetic disorder that almost always occurs in males . Aperson has hemophilia when he or she inherits problems with certain blood- clotting factors, making them unable to work properly . Blood clotting factors are needed to help stop bleeding after acut or injury and to prevent spontaneous bleeding .Types of Hemophilia: 1- Hemophilia A : Is caused by adeficiency of active clotting factor V111 . Factor V111: a protein that participates in acascade of reactions that result in formation of blood clot . The disease arises from amutation in gene for Factor V111 which located on X-chromosome . Is the cause of about 80% of cases . 2- Hemophilia B : Is caused by alack of active clotting Factor 1X .Which makes up the majority of the remaining 20 % of cases .
3- Inherited Metabolic Disorders : Are class of genetic diseases involving disorders of metabolism . The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substrates ) into others ( products ) . In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds . Example of inherited metabolic disorders the metabolism of Phenylalanine and Tyrosine in humans . Albinism , Alkaptonuria
Phenylalanine
PhenylketonuriaPhenylalanine hydroxylase
Tyrosine
Albinism(Tyrosinase –negative type) Tyrosinase
3,4Dihyroxy phenylalanine
-hydroxyphenylpyruric acid Melanin
(Dark pigment in skin and hair)
-hydroxyphenylpyruric Acid oxidase Tyrosinemia
2,5 Dihydroxyphenyl pururic acid (homogentisic acid)
Homogentisic acid oxidase
Alkatonuria
Acetoacetic acid + Fumaric acid
Co2 + H2O
Phenylpyruric acid
Albinism(Tyrosinase –positive type) (Toxic to Central Nervous System)
Tyrosine Tyrosinosis Transaminase
Inherited human disorders with defects in phenylalanine – tyrosine metabolism
Albinism
Alkaptonuria4- Chromosomal abnormality : In these disorder, entire chromosomes or large segments of them are missing or duplicated or otherwise altered . Chromosomal abnormality consist of two types A- Variation in chromosome structure : B- Variation in chromosome number :
- Deficiency (deletion) - Duplication - Inversion - Translocation * Simple * Reciprocal
A- Variation in chromosome structure :A- Variation in chromosome structure :
Autosomal chromosome disorder or cri du chat syndrome : The syndrome associated with a deletion of part of short arm of chromosome 5 . The syndrome includes microcephaly and cat like cry .-Meiotic nondisjunction *Can occur during meiosis I All resulting gametes are aberrant (aneuploid) *Can occur during meiosis II Half of the resulting gametes are aberrant (aneuploid)
B- Variation in chromosome number : Variation in chromosome number results from nondisjunction during meiosis .
B- Variation in chromosome number : Variation in chromosome number consist of two types : Variation in autosomal chromosome number : Variation in sex chromosome number :
Variation in autosomal chromosome number :
1- Down Syndrome ( Mongolism ) : Apatient with Down syndrome has 47 chromosomes instead of 46 chromosomes because Trisomy for chromosome 21 ( three copies of chromosome 21 ) Patient with Down syndrome : Short in stature and had an epicanthalfold, broad short skulls, large tongue, stubby hands, low in mentality .Variation in autosomal chromosome number :
Patau Syndrome ( Trisomy 13 ) : Symptoms include small brain, mental deficiency, deafness Average survival is about 3 month.Variation in autosomal chromosome number :
Edwards Syndrome ( Trisomy 18 ) : Symptoms include fingers overlapping , average survival time is 4 months with death usually caused by pneumonia or heart failure .
Variation in sex chromosome number:
Turner Syndrome : Abnormal female with 45 chromosomes , the sex chromosome is X chromosome only .Variation in sex chromosome number:
Klinefelter Syndrome : Abnormal male with 47 chromosome , the sex chromosomes are XXY . Male who are sterile and in some cases have enlargement of the breast .Variation in sex chromosome number:
Triple X Syndrome : Female with 47 chromosomes , the sex chromosomes are XXX . The female with usually normal genetalia and limited fertility .
5- Somatic Mutation or Cancer :
Cancer is a genetic disease that arises from mutations in genes controlling many aspects of cellular function . All cancer cells share 2 fundamental properties : 1- abnormal cell growth and division ( cell proliferation ) 2- and apropensity to spread and invade other parts of the body ( metastasis ) .Difference between cancer and other genetic diseases :
1- cancer is caused by mutations that occur predominantly in somatic cells . Only 5-10 percent of cancers have ahereditary component . 2- cancers rarely arises from a single mutation, but from the accumulation of many mutations , as many as six to twelve .Blood Groups : Types of Blood groups :
1- Blood group A : Individuals have A antigen on the surface of their red blood cells ( RBCs ). 2- Blood group B : Individuals have B antigen on the surface of their RBCs . 3- Blood group AB : Individuals have both A and B antigens on the surface of their RBCs . 4- Blood group O : Individuals do not have either A or B antigens on the surface of their RBCs . RH System : Individuals have RH ( D ) antigen on the surface of their RBCs .RH- System
Inheritance of Blood groups :
Blood groups are inherited from both parents . ABO blood types is controlled by a single gene called I . it has 3 alleles IA , IB , IO . The gene is located on chromosome 9 . This gene responsible for the producing of the A and B antigens .Table 3 : Genotypes and the Corresponding Phenotypes ( Blood Group Types ) for the ABO Locus in Humans .
47%
O
None
IO IO
3%
AB
Both enzymes
IA IB
8%
B
α-3-D-galactocyltransferase IB IB, IB IO
42%
A
α-3-N-acetyI-D-galactosaminyltransferase IA IA, IA IO
Frequency in Population
Phenotype
Activity
Genotype
For Example : The blood group of the father is A , and the blood group of the mother is O , Give the possible genotypes and blood groups of the children . 1- IA IA Ч IO IO → IA IO IA IO 2- IA IO Ч IO IO → IA IO IO IO The blood group of the children either A or O as in table 2
A, B, AB
A, B, ABA, B, AB
A, B
AB
A, B, AB
O, B
O, A, B, AB
O, B
B
A, B, AB
O, A, B, AB
O, A
O, A
A
A, B
O, B
O, A
O
O
Fathers' Type
AB
B
A
O
Mothers's Type
Blood Type
Rh -
Rh +, Rh -
Rh -
Rh +, Rh -
Rh +, Rh +
Rh +
Father's Type
Rh -
Rh +
Mother's Type
Rh Factor