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Flashcards in Genetics-Mrs Jones Deck (15):

List and explain single congenital abnormalities

Congenital abnormalities are 1:50 newborns, and 25% of death before 10. Genetics are 40% of those
Malformation: Morpholigical defect of part of the body that are intrinsically abnormal (due to genetics)-errors of morphogenesis-like congenital heart defects, or not having a thumb
Disruption: Morphological defects of part of body resulting from extrinsic breakdown or interference with the originally normal process. eg: umbilical cord tied around leg-cant grow well
Deformation: Abnormal form shape or position of part of the body due to exterior mechanical forces. eg: like foot pressed against uterine wall-grow sideways-usually can be fixed
Dysplasia: Abnormal organisation of cell into a tissue and morphological result (like trisomy can develop in later germinal cells-only parts of the body are affected. Eg: Thanatophoric dysplasia: bowed long bones, narrow thorax, large skill. 1:60000-FGFR3 gene


List and explain multiple congenital abnormalities

Sequence: pattern of multiple abnormalities derived from a single known or presumed anomaly eg: Potter sequence, Urogenital causing many other things
Syndrome: Multiple anomalities thought to be pathogenitically related-but not in a sequence (downs syndrome)
Association: Non random occurance in 2 or more individuals of multiple congenital abnormalities not known to be associated
VACTERL ( Vertebral, anal atresia, cardiac defect, tracheaosophageal fistula, esophageal atresia, renal anomalities, limb defects)


Explain chromosome inheritance and define karyotype (explain how chromosomes and gene regions are named)

From each parent you inherit 22 autosomes (chr) and 1 sex chromosome-so you have 23 pairs of chr. Haploid number is 23
Karyotype is an organised way of viewing the 23 pairs to observe any abnormalities
Chr are labelles 1-22 and X and Y. Short arm is called p, then with bands (random now), long arm is called q


Explain the Structural chromosomal abnormalities

Chr abnormalities are present in 60% of misscariages
Structural: duplication of a region, Inversion of a region, deletion, ring arrangement (lose tips and cycle), translocation (bit of one arm exchanged for another (can be on another chr)-robertsonian translocation can be 2 short arms and 2 long arms seperate and come together-make a hybrid chr of 2 long arms. Fine normally but done separate during sex, or can cause fusion protein (BCRABL)


Explain Autosomal Aneuploidy chromosomal defects. Explain trisomy, the most common ones and the main causes

Autosomal aneuploidy is loss or gain of chrs (change in number) -monosomy (loss of 1 chr in a pair), disomy (normal), trisomy (gain 1 chr-can be tolerated), tetrasomy (gain 2 chr-can be tolerated)
16 most common but lethal in utero
13-patau syndrome-heart defect, cleft lip, mental retardation
18: Heart defects, kidney problems, digestive tract defects, mental
21: Downs syndrome
Newborn-hypotonia, lethargy, excess neck skin
Craniofacial-small ears, macroglossia, epicanthic fold
Limbs: single palmear crease, wide gap between 1st and second toe, heart defects, short stature
1:700, but high incidence increase with maternal age
95% are caused by improper seperation, but 4% translocation and 1% mosaicism)
90% maternal orgin chromosome (21), and more likely non disjunction in meiosis 1 (75%), II (25%)
can be caused by translocations-and cause them (robertsonian)-2/3 de novo transloc in child, but 1/3 inherited from patient-if its a chr 14q21q, high incidence of downs syndrome-
Mosaicism-mitotic non disjunction-after fertilised egg duplicates, somwhere down the line one cell becomes trisomy-all its descendeds are-but less affected. Later it happens the better
Why does it cause disease? too much transcription factor/regulation? weird amount of receptors? wierd subunits of proteins?


Explain sex chromosome aneuploidy

Monosomy X: Turners syndrome
1:2000 female birth-lose PATERNAL X/Y
Prenatal-general oedema, swollen neck. Child: Oedomatous hands, WEBBED NECK, low set ears, low hair, broad chest, aotric and urinary defects, short stature-but NORMAL intelligence, can be treated with growth hormone
Kleinfelter syndrome-XXY
pheno MALE, 1:1000-learning disability, taller than average, gynecomastia (large breast), infertile-chr from either parent-rare XXXY or XXXXY


Explain dosage compensation of chromosomes, and its relation to human sex and gender

For x chromosomes, need to ensure males and women get same expression. In humans, random inactivation of one X chr-same in cats-thats why some hairs are difference. Other species double expression of male X (Drosophilia), or decreased X expression in hermaphrodites (C.elegans (XX vs X0)
In humans, male are XY and female XX-but can be chromoscally one and pheno another-because SRY gene controls being a man-so if move to an X, then XX can be male or XY can be female


Explain genomic disorders

genomic disorders are caused by loss or gain of DNA regions
Deletions: Di georges syndrome-microdeletion in 22q-> cardiac abnormality, abnormal face (low ears, widely spaced eyes), cleft palate- CATCH22
Dupliaction: Charcot-Marie-Tooth-microduplic in 17p. Foot drop, distal muscle wasting, foot deformities, absent reflex-treated with surgery and physio


Explain the difference between monogenic and complex diseases, define allele, homologous chr, mutation and polymorphism

Monogenic disease are caused by one gene mutation-clear inheritance, less environement eg: CF, huntingtons, Haemophilia
Complex diseases are the opposite-not one defined genetic cause-no clear inheritence, more environement, less rare eg: T2D, Chrons, Schizophrenia
Allele: Alternate forms of the same gene are the same loci/location-caused by mutations and polymorphism
Homologous Chr are pairs of chr, non identical, with different alleles of the same genes
Mutations are any inheritable change in DNA-missense, nonsense, deletion, insertion (frame shift)-usually kept as mutation for monogenic disease
Polymorphism-mutations that appear in >1% of the pop-usually used for complex diseases


How and why do you take a genetic family history? You can used Mrs Jones as an exemples.
What are the main autosomal inheritance patterns in a tree? give exemples of each

Why? -identify a genetic disease, inheritance pattern, aid diagnosis, management, and relative risk of disease
How: square is male, round is female. Fully dark is affected by disease, round center is carrier. Bar through is dead. sideways line is marrage (double of consangeous), vertical line links to children (left to right in order of age). Twins are showed in a triangle
always build them from the bottom up-usually make sibling of patient, then parents. Then chose one patient and ask about any relative (grandparents, brothers, cousin, nephews/uncles)-record names, maiden names, misscariage, age, death
Main patterns are
Auto Dominant: At least one affected parent, transmitted by M or F to M or F-at least one per generation =>50% of children of affected to be affected
Eg: Huntingtons disease-onset 35-44, surivial after about 20. Huntintin (HTT) gene is mutated to be toxic-can have several copies-more you have worse the disease is (earlier, deadlier)-as you go down generation, have more copies. #of repears>40-defo affected
Auto recessive: No affected parent (necessarily)-skips generation, transmitted by MF to MF-usually no fam history. 25% chance of children of 2 carriers to be carrier, 50% of being carrier-cosanguinity increased chances
Eg: Cytsic Fibrosis. 1:22 carrier in UK, CTFR mutation-affects chloride ions of epithelial cells-thick mucus. Most common is F508
1 gene can cause different mutations in the sexes-Congenital absence of vas deferens (tubes connecting balls to prostate)-can be caused by CTFR mutation


Explain the patterns if inheritance of X Linked disease, and give exemples

X linked Recessive-no affected parents, carrier by F and only affects M-Sons have 50% chance of being affected (if mother chr is their X), Woman have 50% chance of being carrier (chance of being affected-if both parents carrier 25%-v rare tbh)
eg: Haemophillia-blood clotting disorder-2 types A and B. A-F8 coagulation factor VIII-mutated
B-mutations of F9 on X chr, coagulation factor IX (rarer0


Explain and describe genetic heterogeneity, and molecular mechanism of genetic diseases

Same gene different mutation and disease: CAVD and CF with CTFR
Same disease, different genes: haemophilia
Same disease, different genes, different inheritance:Epidermis bullosa can be AR and AD
Incomplete penetrance: Symptoms not always present with disease causing mutation
Variable expressivity-disease severity can vary between people
Phenocopy-same disease but different cause
Epistasis: Interaction between genes causing changing disease phenotypes

Molecular mechanism
Dominant-usually production of toxic protein/molecule (HD)-effects mask the normal copy
Recessive-usually production of non working protein-helped by other copy is carriers-so only if lacking both
Co-Dominant-effect of both normal and disease genes appear in people with both-like sickle cell trait
For therapy: Dominant would want to be turning off the malfunctioning gene, while recessive-want to restore and make activity of the missing gene/protein


Explain, describe and give exemples of genetic imprinting

Genone carries epigenetic markers from its parental origin-75 genes are effected-non mendelian inheritance
These are not genetic-methylation of CpG islands which creates a steric/protein stopping of trancription
The person could have gene 1 imprinted on chr A (dad) and gene 2 of chr B-and has that as adult. With its gametes, the germ cells are not imprinted, but when making sperm-gene 1 on chr A is imprinted, and the gene2 on chr B is imprinted-so when combine to make zygote-same as before
On a tree, maternal imprinting ressembles AR, but rarer.. OFFSPRING of Females carriers( healthy)-50% chance of being carrier
OFFSPRING male are affected if they inherit the faulty gene (50%) -same chance of male/female tho
Chr 15 imprinting disorder: 2 clinically syndrome Paternal Prader Willi, and maternal Angelman
Prader-willi is a paternal imprinting error-obesity, mental impairment, behavioral, muscle hypotonia
Angelman-development delay, movement problems, behavioral uniqueness (happy, ADHD), microencephaly, siezures, strabism, etc
Happens because PWS and As region are close on CHR15-PWS mostly caused by paternal deletion, maternal uniparental disomy (non disjunction leading to 2 paternal chr to be inherited), or paternal imprinting disorder (pat active when it shouldnt)
AS-Deletion of mother genes, paternal unilateral disomy, imprinting defect (mother not active), UB3E mutation
Diagnosis is with FISH, or methylation specific PCR


Explain, describe and give exemples of mitochondrial disorders and inheritance

Mitochondria has own genomes-16.6kB and 37 genes-small-mostly to do with OxPhos and its regulation. 2-10 per mito, and 2000 mito per cell
Always passed down by mother (mito in egg)-but not all mito have same genome-so variable phenotype due to heteroplasmy-how many mutated/affected mitos are transmitted (randomly seperate in meisosis
main diseases: MELAS and LHON
MELAS: Mitochondrial encephalomypathy with lactic acidosis and stroke like episode-progressive, ultimately fatal seizures-mutation of MTTL1-tRNA for Phe replaced by Leu in mito Ribo
LHON: Lebers Hereditary optic neuropathy
more common in males, degeneration of retinal ganlial cells (oxidative damage?)-most mutations in NADH subunits-lost central vision
3 parent babies? Egg and sperm from parent, but remove mito and replace with healthy mito from a 3rd person


Explain describe and give exemples of inborn errors of metabolism

Inborn errors are screened at birth-one gene one defect style-over 200 known-mostly enzyme mutation
UK test for 9, from SCD to PKU and CF and stuff
PKU-Phenylanaline hydrolase deficiency (many different mutations)-blond hair, blue eyes, Eczema, musky odor, if untreated, siezures. Mutations stops excess phenylalanine being made to tyrosine and being dumped in urine or melanin-treatment starts early by eating food with low phenylalanine content, and supllement other AA with meat
MCAD deficiency- Medium chain AcCoa dehydrogeanase-vomiting, acidosis, encephalothy, death
Cant degrate medium length fatty acids-cant really use FAO, hypoglycemia-treated by avoiding fasting and supllements