Genetics Flashcards
what is genetic disease
an illness caused in whole or in part by an abnormality in the individual’s DNA, may be inherited or acquired
are genetic diseases familial
sometimes but not always
environmental disease can also be familial (ie transmittable diseases)
define congenital
present at birth
NOT genetic
are genetic diseases congenital
some but not always
an inherited disease is not always present at birth
environmental disease can be congenital
when can a familial disease be considered to be genetic
if large mendelian pedigree or if not, familial clustering, twin studies, adoption studies
what is familial clustering
familial clustering aims to show the closer the genetic relationship the higher the risk of disease bc the more shared genes= greater chance of that disease
h/e also share environment
what are twin studies
show differences in disease incidence (concordance rate) between MZ and DZ twins as share 100% vs 50% genes
genetically determined diseases show higher concordance MZ than DZ
h/e environment
adoption studies
whether shared genes or shared environment- ie does the adopted child have the disease?
what are diseases that affect onevs multiple genes called
single gene disease
polygenic disease
what are diseases of chromosomes called
what are diseases that involve many genes and the environment called
chromosomal disease
multifactorial disease
a disease of a germline cell leads to (and what is it)
(sperm/ova) an inherited condition
a disease of a somatic cell leads to
(body cells) non-inherited condition
single gene conditions vs complex diseases
single gene conditions are pathological mutations, present only in affected and carriers, significantly alter gene and its protein
complex diseases combination of normal variants present in everyone, subtly alter gene and protein,
how does risk of developing vary between single gene and complex diseases
more positive risk of developing if single gene disease
in complex diseases, genetic susceptibility factors in- ie how good or bad the versions of the gene are but lifestyle influences
PKT
phenyketonuria
autosomal recessive condition, both parents carriers
all tested at birth with Guthrie test
1 in 10000
disease arises due to lack of phenylaline hydroxylase
if know and do not eat phenylaline, no effects. if unaware and eat causes mental retardation, microcephaly, growth failure
karyotyping and normal karyotype
chromosomes are fixed in metaphase when chromosomes have condensed so visible
stain applied, banding used to identify chromosomal abnormalities as there is a unique regular pattern of banding for each chromosome
normal karyotype= 46XX or 46XY
what percentage of all conception have chromosomal abnormality
what percentage of first trimester miscarriages have chromosonal abnormality
7.5% all conceived have chromsomal abnormality
60% of 1st trimester miscarriages have chromsomal abnormality
how many chromsomes are in somatic vs germ cells, what are they otherwise called
somatic cells are diploid, have 46 chromosomes, so 2N.
germ cells (sperm and eggs) are haploid so 23 chromosomes
what is polyploidy
cells with chomsoms in multiples of N greater than 2N
what is aneuploidy
chromsomes NOT in multiples of N, ie missing or extra chromsome
What causes triploidy
Egg fertilised by 2 spermatozoa (dispermy) or by fertilisation of a diploid gamete that arises from failure of maturation
Aneuploidy and polyploidy are what type of chromosomal abnormality?
Numerical
What are the two outcomes of aneuploidy?
Trisomy of that chromosome or monosomy of that chromosome
What is a trisomy
An extra copy of that chromosome, ie downs is a trisomy of 21,,, trisomy 21
What is a monosomy
A loss of a copy of that chromosome is a monosomy of that chromosome
What type of aneuploidy is lethal
All complete monosomies of autosomal chromosomes 1-22 are lethal.
Partial monosomies may survive.
What is the only type of monsomy that is not lethal?
Monosomy X, Turner’s syndrome
What 2 things may aneuploidy result from
Non disjunction
Anaphase lag
What is non disjunction
Failure of chromosomes/sister chromatids to separate at anaphase in cell division
What is anaphase lag
Delayed movement of chromosomes after separation at anaphase
What does non disjunction in meiosis or mitosis result in?
One daughter cell with an extra copy (trisomy) and one daughter cell with a missing copy (monosomy)
What is the result of non disjunction in meiosis 1 and what happens at fertilisation
Meiosis 1 will have one cell with 4 copies of chromosome and one cell will have no copies of chromosome. (Instead of 2 each)
After meiosis 2, there will be 2 cells with 2 copies of the chromosomes and 2 cells with no copies of the chromosome
After fertilisation, 2 cells will be trisomy as sperm adds a chromosome and 2 cells will be monosomic
What happens when there is non disjunction of a chromosome in meiosis 2
1 cell will have 2 copies of chromosome, it’s partner cell will have no copies of chromosome. Next 2 cells will have one copy of chromosome each.
At fertilisation, the cell with 2 copies of chromosome will become trisomic, it’s partner cell will be monosomic, the next 2 cells will be disomic (normal)
What happens if there is non disjunction in meiosis 1 of chromosome 21 of oogenesis
After meiosis 1, one cell will have 4 X chromosomes, one cell will have no X chromosomes
After meiosis 2, first 2 cells will have 2 X chromosomes, next 2 cells will have no X chromosomes
At fertilisation, if an X is added, either of first 2 will become trisomic as 47XXX. Either of the second pair will be monosomic as 45X, Turners.
If a y is added, either of first pair will be trisomic as 47XXY, klinefelters, either of second pair will be monosomic as 45Y, this is lethal
45X is?
Turners syndrome
47XXY is
Klinefelter’s syndrome
Non disjunction of chromosome 21 in meiosis 1 of spermatogenesis results in
At meiosis 1, one cell will have 2X and 2Y, other cell will have none
After meiosis 2, one pair will have XY and one pair will have none
At fertilisation, both XY cells become 47XXY as klinefelters, both cells without will become 45X, turners
Non disjunction of chromosome 21 is more likely lethal in oogenesis or spermatogenesis?
Oogenesis
What happens if there is non disjunction of chromosome 21 in meiosis 2 of spermatogenesis
After meiosis 2 there will either:
be one XX chromosome and one without and next 2 cells will be Y and Y (normal)
At fertilisation, the XX cell will become 47XXX, next 45 X, next 2 normal XY
Or: after meiosis 2 there will be one cell YY, one cell without and 2 normal with an X each
After fertilisation there will be one XYY, one X and 2 normal xx
What is the only way 47XYY can arise
Non disjunction of meiosis 2 in spermatogenesis
What happens if non disjunction of chromosome 21 in mitosis happens early in post fertilisation?
A substantial proportion of cells will have trisomy 21 phenotype
How early this occurs influences how severe (early is severe)
Why do structural chromosomal abnormalities happen
Result from chromosomal breakage and usually involves 1 or 2 chromosomes
May be spontaneous, but rate is increased by exposure to mutagenic agents or inherited conditions with defects in DNA replication
What structural abnormalities may be seen in a single chromsome
Deletion
Inversion
Duplication
Isochromosome
Deletion is what? what type of chromosomal abnormality? occurs in how many chromosomes?
Deletion is a structural abnormality seen in a single chromosome
Deletion is the loss of part of a chromosome
Inversions are what? what type of chromosomal abnormality? occurs in how many chromosomes?
Inversions are structural abnormalities seen in a single chromosome
Inversions are the inversion of a segment of chromosome which may/may not involve the centromere
Duplications are what? what type of chromosomal abnormality? occurs in how many chromosomes?
Duplications are structural abnormalities seen in a single chromosome
Duplication of a chromosomal segment, in tandem or inverse configuration of original sequence
An isochromosome is what? what type of chromosomal abnormality? occurs in how many chromosomes?
An isochromosome is a structural abnormality seen in a single chromosome
An isochromosome is the duplication of 1 arm of that chromosome, coupled with the loss of the other arm, so there are 2 identical arms
What type of structural abnormalities would we see in 2 chromosomes
Insertions
Translocations- reciprocal or robertsonian