Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics 2017 > 17. Complex inheritance (p10) > Flashcards

17. Complex inheritance (p10) Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

Frequency of genetic diseases of different inheritance

A

Chromosomal: 4/1000
Monogenic: 20/1000
Multifactorial: 600/1000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Environmental influence on inheritance

A

Major genes:

  • Monogenic
  • Variable penetrance and expressivity
  • Ecogenetic traits

Minor genes:

  • Polygenic
  • Multifactorial
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Totally genetic diseases examples

A
  • Cystic fibrosis

- Duchenne muscular dystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Characteristics of most of the human traits

A
  • Polygenic
  • Continuous - quantitative traits
  • Additive effects (not dominant and recessive)
  • Multifactorial/complex (environment also involved)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Phenotypes distribution

A

Show continuous, normal distribution in the population.

- As the number of genes increases, so does the number of phenotype categories

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Skin color inheritance

A

Supposing 3 additive genes

- Normal distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Complex disorders (discontinuous)

A

Frequency of diseases shows ethnic group and sex dependency

  • Congenital malformations
  • Chronic adult diseases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Characteristics of multifactorial traits, diseases

A
  • No Mendelian pattern of inheritance (contradicted by concordance in monoz. and diz. twins)
  • Occurs more often in a specific ethnic group and in one gender, but not sex-linked nor sex-limited trait
  • Recurrence risk increase with number of affected children in a family and severity of affected
  • Marriage between relatives moderately increase the risk
  • Risk of affected relatives falls off very quickly with the degree of relationship - First degree relatives of individuals belonging to the more rarely affected gender have a higher risk of bearing the disease)
  • Environment can influence the risk of disease (pos/neg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Methods for indentification of genetic background

A

1) Familial aggregation
2) Twin studies
3) Adoption studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Calculation of familial aggregation

A

λfamily/λpopulation (λr=1 - no genetics, λr>1 - genetics)

λr: relatives
λs: siblings
λp: parents
Example: CF (λs = 750) definitely genetically determined

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

DM inheritance

A
  • Genetic influence in T1DM higher than in T2DM

- Environment affect both types

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How identical are monoz. vs diz. twins?

A

Monoz: 100 %
Dizygotic: 50 %

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Concordance, discordance analysis in twins

A
  • If genetic factors play more important role - concordance of monozygotic will be higher than dizygotic
  • If only environmental factors - concordance values of monozygotic = dizygotic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

2 theories of genes involved in complex inheritance

A

1) Many genes with minor effect

2) Few genes with high penetrance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Identification of genes involved in multifactorial traits, diseases

A

1) Hypothesis driven (linkage analysis)
2) Hypothesis free (GWAS)
* Methods: molecular genetic methods, CGH, microarray etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Finding linkage disequilibrium

A

Two alleles are said to be in linkage disequilibrium if they inherit together more frequently than expected
- Finding genetic markers (SNP, VNTR or known gene)
that inherits together with the given phenotype
*Les mer om linkage equilibrium

17
Q

Haplotype

A

Allele combinations inheriting together (no recombination between them)

18
Q

Congenital malformation: neural tube defects (NTDs)

A

Failure of neural tube closure

  • Spina bifida
  • Anencephaly
  • Higher occurence in Hispanics
  • Reduce risk: folic acid, multivitamins
  • Rates have declined lately - due to screening+diet
19
Q

Effect of folate

A

Folic acid/B9 vitamin

  • DNA methylation => epigenetics
  • DNA synthesis
  • Synthesis of few amino acids
20
Q

Odds ratio, OD

A 
The ratio of the odds of an event (disease) occurring in one group (influenced by a given factor) vs another group (without the factor)
- OD = (A/C) : (B/D)
A: disease+factor
C: disease - factor
B: factor + no disease
D: no factor + no disease
21
Q

T1DM: polymorphisms and mechanisms - HLA

A

HLA-DR/DP (MHC II) and HLA-A/B (MHC I)

  • Significance of some autoantigen-peptides binding to given HLA alleles
  • Autoantigens: preproinsulin, GAD++
  • MHC/peptid combo decreases the central and peripheral tolerance and increases the risk of autoimmune diabetes
  • MHCI and II alleles can be either sensitizing or protective
22
Q

Sensitizing MHCII alleles

A
  • DRB1*0301
  • DQA1*0501
  • B10201/DRB10401-DQA10301-DQB0302
23
Q

Sensitizing MHCI alleles

A
  • HLA-B: B*3906

- HLA-A: A*2402

24
Q

Protective alleles (MHCI?)

A

HLA-B: B*5701

HLA-A: A*1101

25
Q

T1DM: polymorphisms and mechanisms

A

1) HLA-DR/DP (MHCII) and HLA-A/B (MHCI)
2) PTPN22 (prot tyrosine phosphatase, non-R type 22)
3) INS (insulin)
4) IL2RA (IL2 R alpha chain, CD25)
5) CTLA-4 (cytotoxic T-cell Ag 4, CD152)

26
Q

T1DM: polymorphisms and mechanisms - PTPN22

A

Protein tyrosine phosphatase, non-R type 22

  • Regulates T cell activation (dephosp kinases involved in TCR signal transduction)
  • Gain-of-function mutation (AA subst - R620W)
  • Cause abnormal T cell prolif. and cytokine prod.
  • Can be a therapeutic target
27
Q

T1DM: polymorphisms and mechanisms - INS

A

Insulin

  • VNTR polymorphism close to insulin gene
  • Decreased insulin expression in thymus => decreased central tolerance => more autoreactive cells in periph
  • Above caused by Class I alleles, while Class III alleles are protective (and dominant)
28
Q

T1DM: polymorphisms and mechanisms - IL2RA

A

IL2 receptor alpha chain, CD25

  • Mainly expressed in Treg, naive and memory T cells
  • Its regulated expression is involved in supression on T cell response
  • Noncoding variants decrease CD25 expression and disturb T cell regulation
29
Q

T1DM: polymorphisms and mechanisms - CTLA-4

A

Cytotoxic T cell Ag 4, CD 152

  • Inhibitory T cell costim. R
  • Polymorphism at the 3’ end of CTLA-4 gene modify expression level of soluble forms of CTLA-4 => decreased tolerance
30
Q

T1DM - known or suspected environmental factors

A
  • Early childhood events: cow milk, too early nursing
  • Drugs: streptozotocin, pentamidin, interferons, some interleukins
  • Infections: mumps, coxsacckie, rubella, enterovirus, echovirus, sometimes HepB and MMR vaccines
31
Q

Atherosclerosis genes

A
  • ALOX5AP and ALOX5
  • ANGPTL3
  • OX40L or TNFSF4
32
Q

Atherosclerosis genes - ALOX5AP and ALOX5

A

“Arachidonate 5-lipoxygenase-activating protein”

  • ALOX5AP translocates from cytoplasm to the plasmamembrane and activates ALOX5 enzyme
  • ALOX5 synthesizes LTB4 - are in macrophages
  • Macrophages support plaque formation (recruit inflammatory cells)
  • ALOXAP polymorphisms => MI and stroke
  • ALOX5 promoter polymorphisms => ALOX5 expression => CIMT (carotid intima-media thickness)
33
Q

Atherosclerosis genes - ANGPTL3

A

“Angiopoietin-like 3”

  • Polymorphism => coronary atherosclerosis
  • ANGPTL3 inhibits lipoprotein lipase activity => increasing cholesterol and TAG levels
  • Binds to integrin a(v)b(5) => plaque formation (change endothel activation and binding to ECM)
34
Q

Atherosclerosis genes - OX40L or TNFSF4

A

“Tumor necrosis factor ligand superfamily, member 4”

  • In endothels: cross binding of OX40L causes CCL5 chemokine and IL-6 release => T cell and macrophage infiltration => plaque formation
35
Q

Atherosclerosis - known/suspected environmental factors

A
  • Lifestyle: smoking, unbalanced diet, low activity, stress
  • Other diseases: dyslipoproteinemia, diabetes, high blood pressure, obesity, depression (?)
  • Infection: chlamydia pneumonia (?)

Genetics 2017 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions