Syndromes Flashcards
Example of abnormal karyotypes
-Down syndrome (trisomy 21)
-Turner syndrome (monosomy)
-Edward’s syndrome( trisomy 18)
-Palau syndrome (trisomy 13)
Abnormal karyotypes related to non-disjunction sex chromosome
XO (turner)
XXY (Klinefelter)
XYY male
Triple X female
What is the cause of Down syndrome
It is a non-disjunction at the chromosome 21, usually in oogenesis, associated with the age of the mother. Also Robertsonian translocation in familial cases
How common is Down syndrome and whats the foetal loss rate
1/800 live births
30% foetal loss
Symptoms of Down syndrome
-heart malformations
-malformations of GIT
-Mental retardation
-Characteristic facial features
-Increase incidence of leukaemia (10-20X)
-hearing loss
-Many develop neuropathology of alzheimer disease
What is a robertsonian translocation
Chromosome translocate (attaches) to chromosome 14. Results in gametes with a partial trisomy 21 giving Down syndrome. It can also lead to a monosomy of chromosome 21 which is lethal
Trisomy 18 (47, 18+) causes which syndrome and what is the incidence?
Edward’s syndrome
1 in 8000 live births
What is the survival average and foetal loss rate of Edward’s syndrome ?
3 months and 48% foetal loss rate
What is the origin of Edward’s syndrome and the characteristics of these individuals?
It is maternal origin in the 90% of the cases
-microphthalmia
Micrognathia/retrognathia (small backwards jaw)
Microstomia (small mouth)
Low set/ malformed ears
Short sternum
Abnormal clenched fingers
-Rocker bottom feet
Trisomy 13 (47, 13+) is related to which syndrome?
Patau syndrome
What is the origin and incidence of this syndrome ?
It happens 1 in 19000 live births, it is maternal origin in more than 80% of cases
What is the the survival rate and foetal loss for patau syndrome
Survival average of 3 months and 69% of foetal loss rate
What aberration results form a translocation in chromosomes ?
Philadelphia chromosome- it is a reciprocal translocation of C9 and C22 results in Philadelphia chromosome
What does the Philadelphia chromosome produces?
It brings two genes together abl(oncogene) and bcr, creating a new function of the genes turning on an oncogene causing leukaemia. Found in 90% of patients with chronic myeloid leukaemia.
What is a oncogene and what effect does translocations do in these genes?
It is a gene that regulates cell growth, translocations activate oncogenes leading to leukaemia or lymphoma
What are the frequency of birth defects?
10.5% of human newborns carry genes that cause disorders during lifetime
-9 % congenital malformations
1% dominant and X linked
OMIM stands for ?
Online Mendelian inheriatance in Man
Compendium of human genes and genetic phenotypes
How does non-disjunction of sex chromosomes occurs?
It can occur in males and females at meiosis I or II
So gametes could be produced with XX, YY, XY or no sex chromosomes instead of one of either X or Y
44A + Y
Lethal
44A+ X
Turner syndrome 45, XO
44A + XXY
Klinefelter syndrome 47 XXY
44A + XXX
Triple X
44A + XYY
47, XYY
What is the foetal death in Turner syndrome ?
95% of conceptions
What are the characteristics of turner syndrome?
Sterile female phenotype but widely variable
No menstruation
Brown spots
Constriction of aorta
Shortened metacarpal
Poor breast development
What are the causes of Turner syndrome?
80% paternal non-disjunction
Can occur if the second X has a structural abnormality
Non-disjunction in early mitotic division, resulting in mosaics 46:XX; 45,XO
What is the foetal death in Klinefelter syndrome ?
50% of conceptions
1 per 850 live births
What are the characteristics of Klinefelter syndrome XXY
Varies from normal male phenotype to sterile male with breast development
-poor beard growth
-narrow shoulders
-wide hips
-small testicular size
-long legs
Can Klinefelter syndrome also be a mosaic?
Yes! It may occur due tot non-disjunction in early mitotic division. resulting in mosaics 46,XY;47,XXY
What are the characteristics of 47, XXX syndrome?
Usually normal female phenotype, including fertility but some have deleted mental development
TetraX (XXXX) and PentaX (XXXXX) rare, more problems such as mental retardation
What is the origin and incidence of 47,XYY syndrome ?
Always paternal origin at anaphase II or 1?
1 per 1000 live births
What are the characteristics of 47, XYY syndrome
Tall mostly infertile
Predisposition to exhibit behavioural problems, delayed language
What are quantitative traits?
Many genes and each behaving individually in Mendelian fashion, contributing to the phenotype in a cumulative or quantitative way. They are usually a result of polygenic inheritance and is frequently multifactorial
continuous variation
It is measured and described in a quantitative way and is known as quantitative inheritance
How are polygenic traits measured?
They are measured with the help of statistical analysis ANOVA
QTLs are ……
Quantitative trait Loci which are DNA inputs (genes) that contribute to a quantitative trait most of them are protein coding genes, DNA sequences can also contribute to a trait like mutations.
What is the idea behind threshold traits ?
The cumulative effect of multiple alleles, each of small additive effect, may reach the threshold beyond which an abnormal phenotype results. However, this is an artificial idea used for clinical purposes
How did Ronald Fisher described polygenic genes?
Each with multiple alleles, each with a small effect, would sum together to cause a smooth normal distribution in the population
What is narrow sense heritability ?
Serves a measure of how likely an offspring will resemble ist parents, if the heritability is high most of the phenotype is due to additive alleles. (Tall parents will have tall children)
Seed colour that illustrates additive action
Breeding a white plant with a true breeding red plant resulted in 100% progeny of being red. Independent alleles contribute to the red colour. Each gene has an additive and non additive allele. A and B will result in a more intense red colour, heterozygous will lead to an intermediate phenotype. And recessive aabb will be white.
As more quantitative loci become involved…
Grater numbers of classes appear in the F2 generation in more complex ratios five genes are enough to grate a smooth beak shaped curve
Heritability
The proportion of phenotypic traits that can be attributed to genetic variation within certain population
Phenotypic variance has which components
-genotypic variance
-environmental variance
- genotype-by-environment interaction variance
Narrow sense heritability
Proportion attributed to additive gene effects. It’s estimates are valuable for economic traits such a s plant or animal breeders because they estimate the proportion of total phenotype variance for a trait that is due to additive genetic variance.
Is the process of choosing specific individuals with preferred phenotypes form an initially heterogenous population for future breeding.
Artificial selection
This will develop a population containing a high frequency of a desired trait, this sometimes uses back-crossing (sons to mothers etc.)
How can QTLs be mapped ?
Mating homozygous inbred lines that exhibit different phenotypic extremes and examining the expression of QTLs in the F2 generation.
QTLs mapped in humans
Can use pedigree or linkage equilibrium in normal population using genome wide association GWAS and SNP- single nucleotide polymorphisms as markers even spread across the genome.
