1
Sanna Karppinen
13.11.2017
Inheritance patterns II 2
Mitochondrial (lectured elsewhere)
Multifactorial inheritance 2
Untypical ways of inheritance 6
Glossary of terms 15
Faculty of Biochemistry and Molecular Medicine:Molecular, cell biological and genetic aspects of diseases
2
Despite accidents and typical infections heritable elements
are involved in all diseases
• Congenital malformations, common adulthood diseases
• The amount of genetic and environmental factors varies
• Appear in families or in certain population, but inheritance doesn’t
follow any pattern
• polygenic vs. multifactorial?
GENETIC FACTORS
ENVIRONMENT
100%
4. Inheritance patterns II: Multifactorial inheritance
Monogenic vs Multifactorial
In multifactorial diseases
• inheritance pattern is not
so clear, because many
genes and environmental
factors affect the
manifestation
• Pathogenic mechanisms
are complicated
• Etiologic heterogenity:
Same or similar
phenotype may originate
from different factors
4. Inheritance patterns II: Multifactorial inheritance 3
Multifactorial diseases
Disease phenotype
Effect of many genes
“Environmental factors”
Activity
Stress Smoking
other
Gene +
Gene +
Gene -Gene +Gene+
Gene -
S. Solovieva
4. Inheritance patterns II: Multifactorial inheritance 4
Example of epistasisCoat color is controlled by two genes:
• E gene: pigment or no pigment work first
• B gene: the amount of pigment effect depends on E gene
4. Inheritance patterns II: Multifactorial inheritance
These two genes are epistatic,
which means that the expression
of one of the genes is dependent
upon the expression of the other.
5
6
1. DNA repeat expansions and human diseases (will be
lectured as own topic later)
• anticipation = the symptoms of the genetic disorder appear
younger and severity of symptoms increases in each
generation
2. Genomic imprinting
• Expression of a gene is regulated by a parent-of-origin-
specific manner (linked to sex of parent)
• The activity of a gene in a genepair depends on whether
the gene locates in maternal or paternal chromosome
• Methylation of other allele during female/male meiosis:
methylated gene is inactivated• May results in disease, if the only active allele is inactivated or
deleted
• Many are tissue specific
• About 100 genes known, as large groups in genome (e.g.
genes encoding RNA modifying proteins, proteins regulating
tissue growth and brain functions)
CH3
♀ ♂
4. Inheritance patterns II: Untypical ways of inheritance
http://www.geneimprint.com
7
Prader-Willi (PWS) ja Angelman (AS)
syndromes
• frequencies 1:10 000 – 30 000
• Congenital multi-anomaly syndromes
• Genes of the syndromes locate in the same
chromosomal region 15q11-12, 6 imprinted
genes
• Paternal deletion in region 15q11-12 causes
Prader-Willi syndome and maternal deletion
Angelman’s syndrome
• In PWS patients, deletion in paternal
chromosome, mother´s chr inactivated (four
paternally expressed genes)
• In AS patients, deletion in maternal
chromosome, father´s chr inactivated (two
maternally expressed genes)
CH3
♀ ♂
PWS
AS
CH3
♀ ♂
Genomic imprinting
4. Inheritance patterns II: Untypical ways of inheritance
Prader-Willi syndrome (PWS): • PWS gene normally paternally active, maternal inactive• Deletion in paternal allele or both alleles are inherited from mother
(UPD) disease• mild to moderate intellectual impairment and learning disabilities,
obesity, hypogenitals
Angelman syndrome (AS):
• Normally maternal gene active, paternal inactive
• Deletion in maternal allele, or both alleles are inherited from father
(UPD) disease
• delayed development, intellectual disability, severe speech
impairment, and problems with movement and balance
ATP10A
+
4. Inheritance patterns II: Untypical ways of inheritance
Genomic imprinting: Prader-Willi (PWS) ja Angelman (AS) syndromes
8
X-chromosomal inactivation = Lyonization• About two weeks of age in every cell of a
female embryo, one of the two X chrs are inactivated
• Guarantees equal gene dosages both in males and females
• X chr is silenced by packaging it into a transcriptionally inactive structure called heterochromatin
• irreversible → cell herited, similar in every daughter cell (Reversed during oogenesis)
• Females are mosaics: in some cells genes from paternal X-chromosome are expressed and in other cells those from maternal X chr
• If one X-chr contains mutation, part of the cells still have normal allele and gene function
• Not all X-chromosomal genes are inactivated homologs in Y chr
• X-chromosomal inherited diseases: due to abnormal inactivation, a woman carrying X chr recessive trait may manifest the disease (if one X is mutated and the one with normal allele is inactivated in most of the cells)
4. Inheritance patterns II: Untypical ways of inheritance 9
10
Other mechanisms of untypical inheritance:
Prion diseases (will be lectured as own topic later)
Gonadal/germ line mosaikism
• Parent may have mutation in gonads as a mosaic, so that among
the normal germ line cells there is a cell line with altered genome
Uniparental disomy (UPD)
• Person has two copies of a chromosome from one parent and no
copy from the other parent
• Arises from a meiotic chromosome segration defect
(nondisjunction I/II)
• May cause a disease in the case of imprinted genes
4. Inheritance patterns II: Untypical ways of inheritance
Uniparental disomy (UPD)
• Trisomy rescue (loss of onehomologue) can lead to UPD
• UPD can arise also in fertilization, if one gamete is disomic and other nullisomicfor same chromosome
• Child can be homozygous for recessive trait, eventhoughonly one parent has the genedefect being healthy carrier
Cystic fibrosis
4. Inheritance patterns II: Untypical ways of inheritance 11
12
What is the most probable pattern of inheritance in the following pedigrees? Explain why.
Exercise 5.
Questions
• How many genes human have?
• What is a gene?
• Which factors damage DNA?
• What kind of DNA damages there are?
• How different mutations in a gene may affect the gene
product?
• How does dominant/recessive allele affect disease
phenotype?
• X chromosomal inheritance?
• Genomic imprinting, how does it affect disease phenotype?
• What means lyonisation?
• What means uniparental disomy and how it arises?
13
Glossary of terms
• gene locus
• allele
• genotype
• phenotype
• homozygous (AA, aa, +/+, -/-)
• heterozygous (Aa, +/-)
• dominant
• recessive
• autosomal
Gene locus
2 alleles
14
• penetrance
• polymorphism
• X-chromosomal
• carrier
• pedigree
• mitochondrial inheritance
• monogenic
• polygenic (multifactorial inheritance)
• epistasis
Glossary of terms
15
Chromosomal mutations and disorders
Sanna Karppinen
13.11.2017
16
Faculty of Biochemistry and Molecular Medicine:
Molecular, cell biological and genetic aspects of diseases
5 ECTs
17
Chromosomal mutations and disorders 17
Chromosome/genome number changes 20
Errors in the division of chromosomes 24
Autosomal chromosomes 24
Sex chromosomes 34
Structural abnormalities of chromosomes 38
Questions 50
Content of the lecture:
Aims for this part:
• learn the most common chromosomal disorders related
to number changes of autosomes and sex
chromosomes
• get familiar with the different kind of chromosomal
mutations and learn how they arise
18
Chromosomal abnormalities:
• microscopically detectabele change in karyotype
Chromosomal diseases:
• Chromosomal abnormalities lead to excess or loss
of genetic material causing harm for the function orhealthiness of tissue, organ or individual
• Congenital abnormalities, but usually not inheritable
• Develope during fertilisation or before it
• Esiintyvyys riippuu tarkasteluajankohdasta:
• 50% of abortions during first trimester show
chromosomal anomaly
• 0.6% of the live-born have
chromosomal anomaly
• Numerical abnormalities
• Structural abnormalities
4. Chromosomal diseases
• 0.2 % of newborns have a
chromosomal anomaly with
symptoms
• 0.2% symptoms during
childhood or teenage
• 0.2% symptomless changes
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Aneuploidy= abnormal number
of chromosomes
– extra or missing
chromosome(s)
numerical abnormality
Diploid (2N)
Nullisomic (2N-2)
Monosomic(2N-1)
Double monosomic (2N-1-1)
Trisomic (2N+1)
Tetrasomic (2N+2)
Normal set of metaphase chromosomes
Aneuploidy
4. Chromosomal diseases: number changes
Variations in number of complete chromosome sets
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Diplod (2N)
Normal chromosomes
Monoploid - only one set of chromosomes (haploid)
Polyploid - tree or more sets of chromosomes
Triploid (3N))
Tetraploid (4N)
Monoploid (N)
4. Chromosomal diseases: number changes
21
Somatic cell: diploid 2N
Gamete: haploid 1N
Some somatic cells are polyploidic:
• megakaryocytes (16-128n)
• Polyploidy seems to increase thedevelopment of platelets
• hepatocytes (4n-8n)
• Reason is not understood:
prabably for protection of geneticmaterial or gene expression
• Muita kudoksia:
• cardiomyocytes (4n)
• big trofoblasts (8n-64n)
• Purkinjen cells (4n)
• Retinal ganglion cells (4n)
• muscle cells may contain even
hundreds of diploid nuclei in one cell
Cancer cells contain clonal
chromosomal abnormalities
4. Chromosomal diseases: number changes
22
Genome number changes are harmful for embryo development
• Triploidy (3n = 69) may occur, if diploid premature egg cell is fertilised,
or haploid egg is fertilised by two sperm cells at the same time
• Molar pregnancy (non-viable fertilized egg implants in the uterus and
will fail to come to term) may occur from a tsygote having two paternal
and no maternal genome
• Ovarial teratoma: tumor having a diploid egg, which starts to divide
parthenogenetically
• Chimera: fusion of two fertilised tsygotes
• While in monotsygote twins the tsygote divides to form twoembryos developing in uterus separately
4. Chromosomal diseases: number changes
23
Autosomes
• Single number differences in
chromosomes (aneuploidy) are the
most common reasons for both
miscarriages and for chromosomal
disorders
• Defect in meiosis (nondisjunction)
leads to gamete having one
chromosome too much or missing one
chromosome
if this cell participates in
fertilisation, the result is trisomy
(2n=47) tai monosomy (2n=45) for
the corresponding chromosome
• If the defect occurs later → transmitted
to progeny → mosaicism
• Female meiosis is long prone to
chromosomal abnormalities
• Trisomies for chromosomes 13, 18 and
21 are found in live-born babies (and
rare mosaics of trisomies for
chromosomes 8 and 9)
Meiosis I
Meiosis II
Meiosis I
Meiosis II
TRISOMY MONOSOMY
fertilisation
4. Chromosomal diseases: errors in the division of chromosomes
• Defect in I meiotic division:
• Chromosome pair in same pool
diploid ja nullisome gametes
• Errors at meiosis I are the most
common cytologic explanation for
trisomies.
• Most trisomies show a maternal
age effect, and the advanced
maternal age correlates positively
with errors at meiosis I
• 90% chr. 13 ja 21 trisomies:
maternal, generally defects in
meiosis I
trisomic monosomic
gamete
244. Chromosomal diseases: errors in the division of chromosomes
First meiotic division
Defect in II meiotic
division :
• One extra chromosome or
one chromosome loss
• Errors at meiosis II are less
common among
aneuploidies.
• 90% chr.18 trisomies
maternal 2/3 defects in
meiosis II
trisomicmonosomic
gamete
normal
Second meiotic division
254. Chromosomal diseases: errors in the division of chromosomes
26
Trisomy 21, Down syndrome
• incidence 1:600
• often defect in the I division of meiosis, in 80% cases maternal
• The age of mother correlates with the risk of trisomy-21
• about 5 % of the Down patients have trisomy mosaicism,
translocation or other structural defect in the chr 21
• Mosaics have milder symptoms
4. Chromosomal diseases: errors in the division of chromosomes
Exercise 6.
Why mother´s age is associated with higher risk of for a
baby to have chromosome anomalies than with father´s
age?
274. Chromosomal diseases: errors in the division of chromosomes
Trisomy 21, Down syndrome
• Critical genes for the syndrome locate in region
21q22
• 21q22.1-q22.3: 289 genes
• DSCR1 (Down Syndrome Critical Region gene1):
causes intellectual disability and heart defects
• Overexpressed in brains of Down fetuses
• DSCR4: affects development of morphologic
features, hypotonia and intellectual disability
• Expressed mainly in placenta
• Severity of symptoms vary, life time about 40
years (~ 50%)
• Intellectual disability, fastened aging
• Infections, heart problems (not all), dysfunction
of intestinal tract
• Females are fertile, men not
http://www.answers.com/topic/down-syndrome
284. Chromosomal diseases: errors in the division of chromosomes
Function of DSCR1
Nature 441, 582-583(1 June 2006)Normal Down syndrome
DSCR1 and also DYRK1A
29
Protein affects the transcription of genes by inhibiting thecalsineurin dependent signaling pathway and thuspossibly disturbs the development of central nervoussystem
4. Chromosomal diseases: errors in the division of chromosomes
Trisomy 21, Down syndrome
Trisomy 13, Patau syndrome
• 1/10 000 – 20 000
• In 75% of cases extra chr. 13
• translocation 20%, some inherited
• mosaic 5%, incomplete extra chromosome
• Lethal or severe developmental defect• Microcephaly
• Cleft lip and palate
• failure of the forebrain to divide properly
• Severe heart defect
• Abdominal, genital and kidney defects
• Survival about 1-2 months
304. Chromosomal diseases: errors in the division of chromosomes
Trisomy 18 / Edwards syndrome
• More common that trisomy 13, 1: 5000
• ~ 95 % clear trisomies and 5 % mosaic cases
• Partial trisomy 18 due to translocation (~2%)
• Smallest extra region of chr.18 that causes the
syndrome is q21-22
• Brain anomalies , Microcephaly
severe developmental disbility
• Heart defects (~90%)
• clenched hands
• “rocker bottom feet”
• lifetime1-2 months, death latest at 1year of age
314. Chromosomal diseases: errors in the division of chromosomes
Sex chromosomes
• Single number changes or structural abnormalities of sex chromosomes
are less harmful than those in the other chromosomes
• Mostly do not harm embryo development but appear later in the life
• Y chromosome contains low number of genes
• Inactivation of X chromosome
• Sex chromosomes, X and Y, determine the genetic characteristics of sex-linked traits
• SRY-part (pter-q11.2) of Y contains genes that direct the development of
the masculine features without femine phenotype
→ mild developmetal disoders, even harmless, symptoms during
childhood or at teenage
• X and Y share sequence homology segments, pseudoautosomalregions (PAR1, 2, 3)
• inherited in the same manner as autosomes
• in males, pairing and recombination are restricted to the PARs• Deletion of PAR1 is associated with total male sterility
• Reduced recombination in PAR1 can lead to aneuploid sperm, which can cause X-
chromosome monosomy (Turner syndrome) or XXY (Kleinfelter syndrome) in the
offspring
recombination is necessary in males
32
European Journal of Human
Genetics (2008) 16, 771–779
SRY
4. Chromosomal diseases: errors in the division of chromosomes
Sex chromosome
abnormalities
In men:
• 47,XXY (Klinefelter
syndrome)
• 47, XYY
• 46,XY/45,X-mosaicism
In women:
• 45,X-monosomy
(Turner´s syndrome)
• 47,XXX
• 48,XXXX and 49,XXXXX
• 46,XY-naiset
45, X Turner´s syndrome
• 45, X, mosaicism• mosaicism allow the survival in utero: placental rescue cell line
46, XX
• loss of genes in PAR1 affect development of placenta lethality
• Incidence 1: 2500 newborn girls, more common in miscarriages (8.6% vs 0.04%)
• Poorly developed, fibrotic gonads lack of germ cells and ovarian follicles no oocytes
• Activity of two active X chrs are needed to maintain the germ cells and later ovaries
• No estrogen synthesis lack of female features• No puberty without hormone therapy (estrogen and progesterone)
• Somatic abnormalities due to abnormal dosage of PAR genes• Short stature (<150 cm) SHOX important for bone
development and growth
• Lymphedema of the hands and feet
• Heart defect
334. Chromosomal diseases: errors in the division of chromosomes
47, XXY Klinefelter syndrome
• Most common sex chromosome alteration in males
• 47, XXY 1: 500-1000 newborn males
• 48, XXXY, or 49, XXXXY: variant formsmore severe signs and
symptoms
• Extra copies of X chromosome are inactivated
• Extra copies of genes on the X chr. interfere with male sexual
development often prevent testes to function normally
reduce the levels of testosterone
• Affects male physical and cognitive development
• Infertile, small testes
• Slightly feminized physique (breast development, wide hip)
• Poor muscle tone
• Tall stature
• Some have learning and psychological problems
• Testosterone treatment to improve musculine phenotype,
concentration and strenght
• Not inherited
344. Chromosomal diseases: errors in the division of chromosomes
47, XYY
• 1:1000 newborn males
• Affected usually very tall
• severe acne during adolescence
• Fertility and sexual development
are normal normal physical
appearance
• May include learning disabilities
and behavioral problems such
as impulsivity
• Not inherited
354. Chromosomal diseases: errors in the division of chromosomes
36
• DNA damage is common phenomenon in
living cells
• damage occuring during DNA
replication or recombination event may
remain unrepaired or is repaired
incorrectly
• Types of structural abnormalities :
• Balanced: translocations, inversions
• Unbalanced: deletions, duplications,
insertions (occur in all chromosomes)
• Can be inherited, 60-70 %
• unbalanced gametes in meiosis →
disease to progeny
• Geno- and phenotype depends on
how the genetic material of the
parents is divided in meiosis
• Of the clinically relevant cases 1/3
are new alterations, 2/3 inherited
4. Chromosomal diseases: Structural abnormalities of chromosomes
Structural abnormalities of chromosomes
37
Translocationshttps://www.youtube.com/watch?v=MLDCJ2gUC84
• Translocations involve the breakage
and rejoining of two or several
chromosomes
• In balanced translocation there is an
equal exchange of chromosomal
material
Reciprocal translocation: the
location of a gene changes, but the
amount of genetic material is
unaltered
• Doesn’t usually cause problems for a
carrier, but a progeny may be
affected
4. Chromosomal diseases: Structural abnormalities of chromosomes
• Most often either normal or
translocation carrier
chromosomes are inherited• Other distributions lead to
non-balanced chromosomes
miscarriage
38
Examples of translocations
• t(1;8)(q32;q22)
• In Finnish families, > in 10 generations
• Causes miscarriage in 30 % of the pregnancies of carriers
• No chromosomal diseases have been observed in the family
• t(4;11)(q21;p13)
• Normal , can cause problems for progeny
(mixed lineage leukemia)
4. Chromosomal diseases: Structural abnormalities of chromosomes
Example: t(4;11)(q21;p13): meiosis
• Translocation chromosomes have aligned withhomologous chromosome segments in the division planeand a tetravalent is formed.
• What kind of segregation possibilities there are in the I division?
Normal situation
39
Jukka Moilanen (http://www.oppiportti.fi/op/ltg01005/do)
4. Chromosomal diseases: Structural abnormalities of chromosomes
Example: t(4;11)(q21;p13): meiosis
• (A) alternate type balanced chromosomes in gametes
• produces normal gametes, or gametes with the parental balanced translocation. The baby will have a normal phenotype .
• (B, C) adjacent types Association of normal chromosome with rearranged
• gives rise to "duplication-deficiency": an excess of some bits and a lack of other bits → changes in the amount of genes
40
Aalternate type
Badjacent 1 type (frequent)
Cadjacent 2 type, (rare):
normal T carrier Extra 411 deficiency
Extra 114 deficiency
Extra 411 deficiency
Extra 114 deficiency
4. Chromosomal diseases: Structural abnormalities of chromosomes
Robertsonian centric translocation
• Specific type of translocation: fusion of 2 acrocentric chromosomes (chr 13, 14, 15, 21, 22) • Long arms fuse very close to the centromeres rearranged
chromosome includes the long arms (translocation chromosome containing the short arms is lost)
• no phenotypic effect, acarrier has 45 chromosomes but gene dosage does not change
• Frequency 1:1000
• t(13;14)(p10;q10)• carriers 1:1500
• Predisposes to trisomy 13 ja miscarriage, mild infertility
• t(14q;21q), most frequent• In carrier pregnancies 20% risk for extra
copy of chr. 21 (Down syndrome)
414. Chromosomal diseases: Structural abnormalities of chromosomes
lost
42
Chr 14 Chr 21
Normal
chromosomes
Balanced
14/21 carrier
14/21 21 14
21 14
Normal
21
14 deficiency
Lethal
14
21 deficiency
Lethal
14/21 14
Extra 14
Lethal
Possible
gametes
Results in…
14/21
Carrier
14/21 21
Extra 21
Down
4. Chromosomal diseases: Structural abnormalities of chromosomes
• Carrier of the translocation is
phenotypically normal, but has deficiency
in fertility
• Carrier may produce six different types of
gametes
• 1/6 of the gametes have normal
chromosomes, 1/6 has translocation chr
and four are aneuploids
Meiosis in the carrier of Robertsonian transloction t(14;21)
I division I division I division
43
43
Chromosomal abnormalities
have a role in cancer cell
development
t(9;22), Philadelphia
chromosome
• Many known pathological
translocations are balanced
resiprocal translocations
• Philadelphia chromosome: resiprocal
translocation between chr 9 ja 22
t[9,22][q34;q11]
BCR-ABL fusion gene (breakpoint
cluster region Abelson leukemia
viral proto-onkogene)
uncontrollable division of cells,
leukemia
• found only in cancer cells
4. Chromosomal diseases: Structural abnormalities of chromosomes
44
Translocation Associated diseasesFused genes/proteins
First Second
t(8;14)(q24;q32) Burkitt's lymphoma
c-myc on chromosome 8,
gives the fusion protein
lymphocyte-proliferative ability
IGH (immunoglobulin heavy locus) on
chromosome 14,
induces massive transcription of fusion protein
t(11;14)(q13;q32) Mantle cell lymphoma
cyclin D1 on chromosome 11,
gives fusion protein cell-
proliferative ability
IGH (immunoglobulin heavy locus) on
chromosome 14,
induces massive transcription of fusion protein
t(14;18)(q32;q21)Follicular lymphoma (~90% of
cases)
IGH (immunoglobulin heavy
locus) on chromosome 14,
induces massive transcription of
fusion protein
Bcl-2 on chromosome 18,
gives fusion protein anti-apoptotic abilities
t(10;(various))(q11;(various)) Papillary thyroid cancer RET proto-oncogene on
chromosome 10
PTC (Papillary Thyroid Cancer) - Placeholder for
any of several other genes/proteins
t(2;3)(q13;p25) Follicular thyroid cancerPAX8 - paired box gene 8 on
chromosome 2
PPARγ1 (peroxisome proliferator-activated
receptor γ 1) on chromosome 3
t(8;21)(q22;q22)Acute myeloblastic leukemia
with maturationETO on chromosome 8
AML1 on chromosome 21
found in ~7% of new cases of AML, carries a
favorable prognosis and predicts good response
to cytosine arabinoside therapy
t(9;22)(q34;q11) Philadelphia
chromosome
Chronic myelogenous leukemia
(CML), acute lymphoblastic
leukemia (ALL)
Abl1 gene on chromosome 9[15] BCR ("breakpoint cluster region" on
chromosome 22
t(15;17)(q22;q21) Acute promyelocytic leukemia PML protein on chromosome 15
RAR-α on chromosome 17
persistent laboratory detection of the PML-
RARA transcript is strong predictor of relapse
t(12;15)(p13;q25)
Acute myeloid leukemia,
congenital fibrosarcoma,
secretory breast carcinoma,
mammary analogue secretory
carcinoma of salivary glands
TEL on chromosome 12 TrkC receptor on chromosome 15
t(9;12)(p24;p13) CML, ALL JAK on chromosome 9 TEL on chromosome 12
t(12;21)(p12;q22) ALL TEL on chromosome 12 AML1 on chromosome 21
t(11;18)(q21;q21) MALT lymphoma API-2 MLT
t(1;11)(q42.1;q14.3) Schizophrenia
t(2;5)(p23;q35) Anaplastic large cell lymphoma ALK NPM1
t(11;22)(q24;q11.2-12) Ewing's sarcoma FLI1 EWS
t(17;22)dermatofibrosarcoma
protuberansCollagen I on chromosome 17
Platelet derived growth factor B on chromosome
22
4. Chromosomal diseases: Structural abnormalities of chromosomes
Translocations in cancer
Unbalanced translocation
• Unequal exchange of chromosome material
extra or missing genes = deletions and duplications
• Extra gene material (>4%) or missing material(>2%): miscarriage
• Small alteration (microdeletion/ duplication): chromosome disease
• Usually sporadic, with mild phenotype, inheritablechanges
•Deletions of short arm of chr. 4 and 5: intellectualdisability
•Prader-Will: 15q11-13 paternal deletion
• intellectual disability, over-weight, special features
•Angelman syndrome: 15q11-13, maternal deletion
• severe intellectual disability, epilepsy, anxiety, specialfeatures
454. Chromosomal diseases: Structural abnormalities of chromosomes
Inversions• If two breaks occur in one
chromosome
the region between the breaks
may rotate 180 degrees before
rejoining with the two end fragments
the overall amount of the genetic
material is not changed
• inv9(p11;q13), most common in
general population, 1 -3%,
• always inherited as an balanced
form
• no recombination
• clinically inrelevant
• Clinically relevant appear in the
cases of infertility or
phenotypically abnormal child
464. Chromosomal diseases: Structural abnormalities of chromosomes
• Recombination doesn’t
happen in short inversion
• In long inversions,
inversion chromosome
aligns with homologous
chromosome
inversion loop
crossing-over
deletions or duplications
474. Chromosomal diseases: Structural abnormalities of chromosomes
Inversions
Questions• What effects can extra chromosomal material have?
• What means Robertson´s translocation?
• How can be a Down syndrome inherited from a parent
to child?
• What happens in reciprocal translocation?
• What means unbalanced translocation?
• What is a Philadelphia chromosome?
48