3rd Class

Question 1

Definition allele

Answer 1

Variant of a given gene that occupies the same site on the homologous chromosome

Question 2

Definition locus

Answer 2

Place the chromosome where the allele is located

Question 3

Definition genotype

Answer 3

Complete genetic information (set of genes) about an individual

Question 4

Phenotype

Answer 4

Set of features that make up the morphological and functional whole.of given individual organism

Question 5

Homozygous

Answer 5

A person who carries two identical alleles at a specified locus

Question 6

Complex heterozygous

Answer 6

A person who has two different mutations in the same gene on homologous chromosomes

Question 7

Hemizygous

Answer 7

A Male carrying only one allele of a given associated with the X chromosome (with some exception of the pseudoautomosomal regions)

Question 8

Allelic heterogenicity

Answer 8

Presentce of different mutations within the same gene

Question 9

Autosomal dominant inheritance

Answer 9

Phenotype will be expressed in those who receive only one copy

Question 10

Autosomal dominant % probably of kids that will be ill

Answer 10

50%

Question 11

Penetrance

Answer 11

How genotype is translated to phenotype. If the gene will be expressed or not. May be 100% so everyone that have the gene will be affected. Or 50% so half will be affected

Example braca 1 mutations - hereditary breast ovarian cancer, symptoms will only be expressed in females

Question 12

Expressivity

Answer 12

How much the trait affects or how many will be affected. Variable or stable (100% same in every affected person)

Stable - Dwarfism - achondroplasia - bone deformation. Penetrance is 100% but stable expressivity - the same clinical picture

Variable - Neurofibromatosis type 1 - expressivity is variable, some develop very severe, other may not have any neurological signs

Question 13

Cafe au lait spots

Answer 13

At least 6 to diagnose NF1. Only visible, dark brown spots on skin

Question 14

Lisch nodules

Answer 14

Non malignant tumors- in the iris, brown spots

Common trade of NF1 disease

Question 15

Diagnosis criteria for neurofibromatous 1

Answer 15

6 or more cafe au lait macules
2 or more skin neurofibromas
Crewe sign - axillary or groin freckling
optic pathway glioma
2 or more lisch nodules
bony dysplasia 
first degree relative with NF1

Question 16

Neurofibromatosis type 1 definition

Answer 16

Mutation on chromosome 17, autosomal dominant or spontanous mutation, encodes for neurofibromin, Ras pathway, GTPse

Protein regulation of cell division

Nf1 is tumour suppressing gene

Question 17

Huntington disease when is the onset of symptoms?

Answer 17

Onset of symptoms is middle age

Question 18

Chorea

Answer 18

Involuntary movements, mostly in lower legs, eyes (closing opening) face muscles and tongue

Question 19

Dysarthria

Answer 19

slurred speech bc of muscle weakness

Question 20

Mutation Huntington disease

Answer 20

Autosomal dominant
Chromosome 4 - protein huntingtin
Molecular dynamic mutation - some of the regions where dinucleotide repeats in a gene for the disease there is a region with 3x CAG - in Huntington we have polyglutamine above the normal

normally CAG repeats = 10-26
between 26-36 = not symptoms but increased instability → number of repeats may increase between
31-36 = Huntington with incomplete penentrance
• > 36 = Huntington
• > 40 = complete penentrance
• > 80 = juvenile – get it before 18 → parkinson like → cognitive decline + behavioral problems,
stiffness, slowness, incoordination
• adult 36-55 CAG, early onset = 60 CAG

Question 21

Anticipation

Answer 21

Seen in families dealing with dynamic mutations , where we observe more mutations from generation to generation. Where it develops earlier and more severe

Question 22

Autosomal recessive %

Answer 22

25%

Question 23

Autosomal dominant %

Answer 23

50 %

Question 24

Nf1 diagnosis

Answer 24

Clinical findings and DNA - based testing for NF1 gene 17q11

Question 25

Huntington disease - symptoms

Answer 25

``` Chorea Dystonia Incoordination cognitive decline Behavioural difficulties Starts mild with mood swings, depression ```

Question 26

What does genetic anticipation mean?

Answer 26

Genetic anticipation is a phenomenon in which the signs and symptoms of genetic conditions become more severe and/or appear at an earlier age ex Huntington disease

Question 27

Neurofibromatosis type I other name

Answer 27

Recklinghausen's disease

Question 28

Neurofibromatosis type I mutation

Answer 28

autosomal dominant | 90% point mutation, 17q 11.2

Question 29

Duchenne Muscular dystrophy - type of mutation

Answer 29

X-linked recessive Xp21.3-21.2 Lack of dystrophin production

Question 30

Duchenne Muscular Dystrophy - symptoms

Answer 30

falling, fatigue, weakness in shoulders & pelvis, muscle waste, Gower sign, lordosis, swollen calfs, waddling gait skeletal defects, mental disability, loss of walk, respiratory failure, paralysis

Question 31

X linked recessive - penetrance is 100% in ? (female/male)

Answer 31

Male, bc only one copy of X chromosome

Question 32

DMD - age of onset

Answer 32

around 5 years old

Question 33

BMD - age of onset

Answer 33

11 years

Question 34

Becker muscular dystrophy - mutation

Answer 34

point mutation in frame mutation, multiple of 3 bases deleted or duplicated

Question 35

Fragile X syndrome - other name

Answer 35

Martin - Bell syndrome

Question 36

Fragile X syndrome - mutation

Answer 36

X linked recessive Mutation in FMR1 gene - no FMR protein also mutation in FRAXE but less common CGG repeats at Xq27: Normal: 6-40 Affected: more than 200 At risk: 40 - 200 - don´t display the syndrome In affected: the gene is methylated and there is no expression

Question 37

Fragile X syndrome symptoms

Answer 37

Large protruding ears Postpubescens macroorchidism (large testis after puberty) high arched palate hyperextensible finger joints hand flapping, shyness, limited eye contact -autism ADHD behavioral problems Mental retardation speech problems overactivity & impulsiveness → stereotypic repetitive behaviours (handflapping, strong preoccupation & fascination)

Question 38

What is the difference in mutations of DMD and BMD

Answer 38

DMD mutations cause deletions and duplications - frame-shifts Dystrophin is absent in DMD BMD cause in-frame alterations (multiple of three bases is deleted or duplicated) Dystrophin present in reduced quantity in BMD patients

Question 39

Hemizygous definition

Answer 39

Refers to a gene that is present in only a single copy (hemi = “half ”). Most com- monly refers to genes on the single male X chromosome but can refer to other genes in the haploid state, such as the genes homolo- gous to a deleted region of a chromosome.

Question 40

heterogeneity, allelic

Answer 40

Describes conditions in which different alleles at a locus can produce variable expression of a disease. Depending on phenotype definition, allelic heterogeneity can cause two distinct diseases, as in Duchenne and Becker muscular dystrophy.

Question 41

heterozygote

Answer 41

heterozygote An individual who has two different alleles at a locus. Compare with homozygote

Question 42

homologous

Answer 42

(1) Refers to DNA or amino acid sequences that are highly similar to one another. (2) Describes chromosomes that pair during meiosis, one derived from the individual’s father and the other from the mother

Question 43

homozygote

Answer 43

An individual in whom the two alleles at a locus are the same. Compare with heterozygote.

Question 44

Spinal muscular atrophy - mutation

Answer 44

Autosomal recessive | Homozygous deletion of SMN1 gene (survival motor neuron 1) on chromosome 5

Question 45

Spinal muscular atrophy symptoms

Answer 45

Weaking of muscles due to degeneration of alfa motor neurons - atrophy hypotonia, scoliosis, thin limbs severe: respiratory failure, death

Question 46

DMD pathogenesis

Answer 46

Dystrophin protein + complex + intracellular actin + ECM - stabilazes sarcolemma its dysfunction cause leakage of createnin kinase out, calcium in, muscle death