Lesson 8 Flashcards
Classifications of Genetic Diseases
Classification of genetic Diseases
- Single Gene Defects (Mendelian)
- Disorders with Multifactorial (Polygenic)
- Cytogenetic Disorders
- Disorders showing Atypical Patterns of Inheritance
Consequences of genome abnormality or mutation in a single gene; could be heritable/non-heritable and are visible since birth.
Single Gene Defects (Mendelian)
Types of Mendelian Disorders
- Autosomal (dom/rec)
- X-linked (dom/rec)
- Mitochondrial
Difference between Autosomal Dominant and Recessive mutations
Dom: expressed when only 1 copy of that mutation is present
Rec: requires 2 mutated copies for disease to develop
Difference between X-linked Dominant and Recessive mutations
Dom: Father = daughter
Mother = daughter & son
Rec: Father = carrier daughter (all unaffected)
Mother = only son affected; carrier daughter
Can affect both males and females but ONLY PASSED ON FEMALES; can appear in every generation
Mitochondrial
Huntington’s
Neurofibromatosis
Achondroplasia
Familial hypercholesterolemia
Autosomal Dominant
Tay-Sachs
Sickle cell anemia
Cystic fibrosis
Phenylketonuria (PKU)
Autosomal Recessive
Hypophatemic rickets (vit D res)
Ornithine transcarbamylase def
X-linked Dominant
Hemophilia A
Duchenne muscular dystrophy
X-linked Recessive
Leber’s hereditary optic neuropathy
Kearns-Sayre syndrome
Mitochondrial
An inherited condition that causes progressive degeneration of neurons in the brain
Huntington’s Disease
Cause of Mutation in Huntington’s Disease
HTT gene mutation (the CAG trinucleotide repeat)
A condition characterized by the formation of multiple neurofibromata and possible neuromas
Neurofibromatosis
Cause of Mutation in Neurofibromatosis
a change in the NF1 gene
inherited disease in which the muscles contract but have a decreasing ability to relax
Myotonic dystrophy
DMPK gene or CNBP gene
Cause of Mutation in Myotonic dystrophy
A genetic disorder of the red blood cell membrane that is characterized by the anemia, jaundice, and enlargement of the spleen
Hereditary spherocytosis
ANK1, SLC4A1, SPTB, or EPB42
Cause of mutation in Hereditary spherocytosis
An inherited bleeding disorder, in which clotting protein called von Willebrand factor is deficient or defective
Von Willebrands Disease
Cause of Mutation in Von Willebrands Disease
VWF gene
An inherited type of hyperlipidemia in which it is recognizable in childhood and due to the genetic defects in receptors and LDL
Familial hypercholesterolemia
LDLR gene, APOB gene, or PCSK9 gene
Cause of mutation in Familial hypercholesterolemia
A genetic disease characterized by acute neurovisceral attacks
Acute Intermittent porphyria
Cause of Mutation in Acute Intermittent porphyria
gene coding in HMBS
A heritable disorder of connective tissue that is characterized by easy bruising, joint hypermobility, skin laxity, and weakness of tissue
Ehler-Danlos Syndrome
COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, FKBP14 or ADAMTS2 gene
Cause of Mutation in Ehler-Danlos Syndrome
An inherited disorder of connective tissue that is charactized by abnormalities of the eyes, skeleton, and cardiovascular system
Marfan’s Syndrome
Cause of mutation in Marfan’s Syndrome
change in the FBN1 gene
A metabolic disease that is due to the inherited inability process the essential amino acid phenylanine
Phenylketonuria
Cause of mutation in Phenylketonuria
change in the PAH gene
A genetic disease that affects the exocrine glands and is characterized by the production of abnormal secretions
Cystic fibrosis
Cause of mutation in Cystic Fibrosis
gene CFTR (cystic fibrosis transmembrane conductance regulator) protein
A genetic blood disorder caused by the presence of an abnormal, sickle shaped form of hemoglobin
Sickle Cell Anemia
Cause of mutation in Sickle Cell Anemia
hemoglobin-Beta gene found in chromosome 11
An inherited disorder that causes progressive muscle weakness and loss of muscle mass
Duchenne Muscular Dystrophy
changes of the DMD gene on the X chromosome
Duchenne Muscular Dystrophy
An inherited disorder in which the ability of blood to clot normally is impaired
Hemophilia
Cause of mutation in Hemophilia
genetic changes in the F8 gene
The cause are the defects in multiple genes coupled with environmental factors
Multifactorial genetic disorders
Mutation in chromosome 19
Alzheimer’s disease
Code for stabilization the microtubule
Chromosome 19
Abnormal clumps of cellular debris and protein (plaques) and collapsed microtubules
Alzheimer’s
Mutation in chromosome 5
Colon cancer
Code for prevention of uncontrolled cell growth
Chromosome 5
Develop growths called polyps in their colon; when not treated will develop into cancer
Colon cancer
Mutation on chromosome 13 and 17
Breast cancer
Code for tumor suppressor genes because they prevent uncontrolled cell growth
Chromosome 13 and 17
Uncontrolled cell growth and cancer
Breast cancer
Mutation on chromosome 2
Hypothyroidism
Code for thyroid hormone production
Chromosome 2
Altered production of thyroid hormone
Hypothyroidism
Chromosomal aberrations in Cytogenetic Disorders vary in chromosome ___________
Structure and number
Structural Aberration
- Deletion (deficiency)
- Duplication (Repeat)
- Inversion
- Translocation
Two types of Deletion
Terminal
Interstitial (intercalary)
4 Types of Duplication
Tandem
Reverse tandem
Displaced
Translocation
2 Classification of Inversion
Paracentric
Pericentric
Classification of Translocation
Simple
Shift
Reciprocal
Balanced
Unbalanced
Numerical Aberration
Euploidy
Aneuploidy
Classification of Aneuploidy
Nullisomy
Monosomy
Trisomy
Tetrasomy
Chromosome structure can be altered in two primary ways:
- Change in amount
- Rearrangement
Loss of chromosome segment
Deletion
Results from single break near the end of the chromosome
Terminal deletion
Two sections may be deleted if two breaks occur
Interstitial
Deletion Cytogenetic Disorder
Cri-du-chat
Chronic myelocytic leukemia
Prader-Willi syndrome
Occurrence of an additional chromosome segment
Duplication
Occurs when the extra chromosome segment is somewhat located immediately after the normal segment in precisely the SAME ORIENTATION
Tandem
When the gene sequence in the extra segment of a tandem is in reverse position
Reverse tandem
Occurs when the extra segment may be located in the same chromosome but away from the normal segment
Displaced
When the additional segment is located in a non-homologous chromosome
Translocation
Duplication Cytogenetic Disorder
Charcot-Marie-tooth disease
Occurs when a segment of chromosome is oriented in the reverse direction and such segment is said to be inverted
Inversion
If the inverted INCLUDES the centromere
Paracentric
If the inverted area DOES NOT INCLUDE the centromere
Pericentric
Wherein a gene is repositioned in a way that alters its normal level of gene expression
Position effect
Inversion Cytogenetic Disorder
Hemophilia type A
It is the integration of a chromosome segment into a non-homologous chromosome
Translocation
Terminal segment of a chromosome is integrated at ONE END of a non-homologous chromosome
Simple
An intercalary segment of a chromosome is integrated WITHIN a non-homologous chromosome
Shift
Produced when two non-homologous chromosomes EXCHANGE segments or when segments are reciprocally transferred
Reciprocal
NO phenotypic consequences
Balanced
ASSOCIATED WITH phenotypic abnormalities and sometimes death
Unbalanced
Example of Unbalanced
familial Down syndrome
Variation in the number of SETS of chromosomes
Euploidy
Variation in the number of A PARTICULAR chromosome
Aneuploidy
Loss or gain of one or more chromosome
Aneuploidy
Loss of ONE HOMOLOGOUS chromosome
Nullisomy (2n-2)
Loss of a SINGLE chromosome
Monosomy (2n-1)
ONE EXTRA chromosome
Trisomy (2n+1)
one EXTRA chromosome PAIR
Tetrasomy (2n+2)
Cat cry syndrome
Microcephaly
Broad face, saddle nose
retardation (mental & physical)
Cri-du-chat Syndrome
Deficiency in the SHORT arm of chromosome 5
Cri-du-chat Syndrome
Deletion of chromosome 22 (Philadelphia chromosome)
Chronic myelocytic leukemia
Deletion on the LONG arm of chromosome 15
Prader-Willi syndrome
Small duplication in the SHORT arm of chromosome 17 = peripheral neuropathy
Charcot-Marie-tooth disease
Inversion disrupting the gene for factor VIII
Hemophilia type A
Occurs as an exchange of genetic material between chromosome 9 and 22
Chronic Myelogenous Leukemia
“Mongolism”
short stature, epicanthal fold, broad short skulls, wild nostrils
EXTRA chromosome 21
Down Syndrome
Trisomy 21 wherein LONG arm of chromosome 21 joins with long arm of chromosome 14 or 15
Robertsonian translocation
Arises when carrier parents (heterozygotes) mate with normal parents
Familial Down Syndrome
Trisomy 13 (47+13)
mental retardation, growth failure, low set deformed ears, deafness, polydactyl
Patau’s Syndrome
Trisomy 18 (47+18)
open skull sutures at birth, rocker bottom feet, high arched eyebrows
Edward’s Syndrome
Product of nondisjunction during gametogenesis
Results from MONOSOMY of SEX chromosomes in FEMALES (45, XO)
Turner’s Syndrome
Exhibit chromosome
47, XXY
48, XXXY
48, XXYY
49, XXXXY
50, XXXXXY
Klinefelter’s Syndrome
Females with THREE or MORE X chromosomes
Poly-X females (44XXX)
Occurs in males resulting from nondisjunction during spermatogenesis
Jacob’s Syndrome (44XYY)
