Molecular Genetics Flashcards
What are chromosomes 1-22?
Autosomes
What is the 23rd chromosome pair?
Sex chromosomes
What are males?
XY
What are females?
XX
What are alleles?
Different forms of one gene
What are allotypes?
Different forms of one protein
What is polymorphic?
Alternative forms of one gene = many alleles
What is oligomorphic?
Few forms of one gene = few alleles
What is monomorphic?
No polymorphism
What is homozygous?
Same allele on both inherited chromosomes
What is heterozygous?
Different allele on both inherited chromosomes
Describe mitosis
Division of somatic cells
2 daughter cells from 1 parent cell
What does not change in mitosis?
No. of chromosomes
When does the DNA duplicate in mitosis?
Before entering mitosis
Describe meiosis
Division of germline cells
Only in gamete formation
1 diploidic cell produces 4 haploid gametocytes
How many chromosome do cells have in mitosis?
46 chromosomes (2n)
How many chromosome do cells have in meiosis?
23 chromosomes (n)
What is a mutation?
Change in genetic material
What are the basic types of DNA mutation?
Missense mutation = different amino acid
Nonsense mutation = chunkated protein
Frameshift mutation
What are the classes of genetic diseases?
Chromosomal disorders
Monogenic disorders
Multifactorial disorders
Polygenic disorder
Somatic disorders
Mitochondrial disorders
What is an example of a chromosomal disorder?
Down syndrome
What is an example of monogenic chromosomal disorder?
Cystic fibrosis
Sickle cell anaemia
Haemophilia A
What is an example of multifactorial disorder?
Ischemic heart disease
What are monogenic (single gene) disorders caused by?
Change in just one or both copies of particular pair of genes
What is autosomal dominant?
One chromosome affected
(heterozygote)
What is autosomal recessive?
Both chromosomes affected
(homozygous)
What is X-linked?
Mutation on X chromosome
What are examples of autosomal dominant inheritance?
Huntington disease
Marfan syndrome
For it to be autosomal recessive what must happen?
BOTH parents need to be a carrier
What are examples of autosomal recessive disorder?
Sickle cell disease
CF
Spinal muscular atrophy
If you’re a carrier of sickle cell disease, what will happen?
Small changes in haemoglobin shape
BUT doesn’t effect O take up
Describe autosomal dominant
Heterozygote (Aa) or homozygote (AA)
Least 1 affected parent
Describe autosomal dominant: achondroplasia
Change in transmembrane domain of FGFR3
What is FGFR3 involved in?
Cartilage to bone transition
What does achondroplasia do?
Inhibits bone growth
Describe autosomal recessive
Very rare
Homozygote (aa)
Describe autosomal recessive: sickle cell anaemia
Single nucleotide substitution
What happens to haemoglobin in patients with sickle cell anaemia?
Hb polymerises under low O
=distorts RBC shape
= affects O transport
What is the vaso-occlusive/pain crisis?
Distorted RBC shape
= gets stuck
= blocks blood vessel
= pain
What is dactylitis?
Painful swelling of hands + feet which occurs in infants
Describe autosomal recessive: CF
Mutation in CFTR gene
What is it if 2 affected people have an unaffected child?
Dominant pedigree
Aa = parents
aa = child
What is it if 2 unaffected people have an affected child?
Recessive pedigree
Aa= parents
aa = child
What are examples of X-linked recessive?
Haemophilia
Fragile X syndrome
Describe X-linked recessive
Acts as recessive traits in females (XX)
Dominant traits in males (XY)
Describe X-linked recessive: haemophilia
B = deficiency factor IX
A = deficiency factor VIII
Inversion mutation
What is an inversion mutation?
Genetic sequence flipped after duplication
What are the management of haemophilia?
Joint immobilisation + physical therapy
COX-2 inhibitors
Describe X-linked dominant
BOTH male + female affected
What is an example of X-linked dominant?
Rett syndrome
Describe Rett syndrome
X-linked MECP2
Loss of language, cognitive + motor abilities
Describe Y-linked dominant
Very rare = sex-linked
Mutations on Y chromosome
Describe mitochondrial inheritance
Mitochondrial DNA inherited only through egg
What is polygenic inheritance?
Trait coded by a number of altered + unaltered genes working together
What are examples of polygenic inheritance?
Alzheimer’s
Diabetes
Cancer
Eczema
What are examples of congenital malformations of multifactorial disorders?
Cleft lip
Heart defects
What are examples of adult onset disorders of multifactorial disorders?
Diabetes
Epilepsy
Hypertension
Ischaemic HD
Glaucoma
What are numerical chromosome abnormalities?
Gain or loss of complete chromosomes
What is the common cause of numerical chromosome abnormalities?
Non-disjunction
What are the chromosome aberrations?
Deletion
Translocation
Inversion
What is translocation?
Section shifts from one chromosome to another
What is inversion?
Section gets snipped off + reinserted the wrong way around
What is a terminal deletion?
Removed off end
What is an interstitial deletion?
Deleted from the middle
What is autosomal trisomy?
When a chromosome has an extra copy
Describe autosomal trisomy: down syndrome
Trisomy 21
Describe autosomal trisomy: Edwards syndrome
Trisomy 18
Multiple malformations
90% die before 5 months
Describe autosomal trisomy: Patau syndrome
Trisomy 13
Multiple malformations
Most die few weeks after birth
Describe anomalies of sex chromosome number: klinefelter syndrome
XXY
Males
Infertility = do NOT produce sperm
Describe anomalies of sex chromosome number: Turner syndrome
X
Females
What are the possible treatment for genetic diseases?
Correct metabolic consequences
Replace absent enzyme
Remove excess stored product
Correct basic genetic abnormality
What are the different types of gene therapy?
Replacement
Correction
Augmentation
What is replacement gene therapy?
Mutant gene removed + replaced with a normal gene
What is correction gene therapy?
Mutated area of affected gene would be corrected + remainder left unchanged
What is augmentation gene therapy?
Introduction of foreign genetic material into cell to compensate for defective product of mutant gene
