Variations in Chromosome Number and Arrangement

Variations in Chromosome Number and Arrangement

* Chromosomal mutations or aberrations
o Abnormal chromosomal number
o Gene deletion or duplication
o Chromosome rearrangements
* Aberrant chromosomes passed on in a Mendelian fashion

Terminology
* Euploid – chromosomes present in complete haploid units
o Haploid
o Diploid
o Triploid
o Tetraploid
* Aneuploid – loss or gain of one or more chromosomes
* Alloploid – multiples of different genomes

Aneuploidy
* Commonly results from nondisjunction during meiosis
o Monosomy, trisomy, tetrasomy, etc.
o Klinefelter and Turner syndromes are examples involving human sex chromosomes

Nondisjunction
Monosomy
Cri-du-Chat Syndrome
* Autosomal monosomy in humans not reported beyond birth (die quickly)
* Partial autosomal monosomy may survive
* “Cry of cat” syndrome

Trisomy
* Trisomy (2n + 1)
* Meiotic issues

Trisomy Meiosis
Down Syndrome
* Discovered in 1866 by John Langdon Down
* Now known to result from trisomy 21 (47 +21)
* One per 800 live births
* 75% due to nondisjunction in meiosis I
* Ovum is source of extra 21 in 95% of cases

Down Syndrome – Trisomy 21
Maternal Age and Down Syndrome
Patau Syndrome
Edwards Syndrome
Viability in Human Aneuploidy
More From the Carr Study
Polyploidy in Plants
Autopolyploidy
Experimentally Produced Tetraploids
Yeast Models
Allopolyploidy
Allotetraploid Formation
Allotetraploids
Wheat/Rye Cross
Somatic Cell Hybridization
Protoplast Fusions
Endopolyploidy
Chromosome Rearrangements
Consequences of Rearrangements
Deletions
Compensation Loop in a Polytene Chromosome
Duplications
Unequal Crossing Over
Position Effects
Gene Duplication and Evolution
Chromosomal Inversions
Inversions and Gametogenesis
Inversions and Recombination
Translocations
Familial Down Syndrome
Fragile Sites
Fragile X Syndrome
Fragile X Chromosomes

Variations in Chromosome Number and Arrangement.ppt

Read more...

Reasons for Referral to Genetics

Reasons for Referral to Genetics

Prenatal or preconceptional patient who is or will be:
* Age 35 years or older at the time of delivery (for a singleton pregnancy)
* Age 33 years or older at the time of delivery (for a twin pregnancy)
* A close blood relative of her partner (consanguineous union)

Prenatal or preconceptional patient who has:
* An abnormal first or second trimester maternal serum nuchal translucency screening test
* Exposure to a teratogen or potentially teratogenic agent during gestation such as radiation, high-risk infections (cytomegalovirus, toxoplasmosis, rubella), drugs, medications, alcohol, etc.
* A fetal anomaly or multiple anomalies identified on ultrasound and/or through echocardiography
* A personal or family history of pregnancy complications known to be associated with genetic factors such as acute fatty liver of pregnancy

Either member of the couple with:
* A positive carrier screening test for a genetic condition such as cystic fibrosis, thalassemia, sickle cell anemia, Tay-Sachs, etc.
* A personal history of stillbirths, previous child with hydrops, recurrent pregnancy losses (more than two), or a child with sudden infant death syndrome (SIDS)
* A progressive neurologic condition known to be genetically determined such as a peripheral neuropathy, unexplained myopathy, progressive ataxia, early onset dementia, or a familial movement disorder
* A statin-induced myopathy

Either member of the couple with a family or personal history of:
* A birth defect such as a cleft lip palate, spina bifida, or a congenital heart defect
* A chromosomal abnormality such as a translocation, marker chromosome, or chromosomal mosaicism
* Significant hearing or vision loss thought to be genetically determined
* Mental retardation or autism

Genetic consultation may be helpful under the following circumstances for adult patients with a personal history of:
* Abnormal sexual maturation or delayed puberty
* Recurrent pregnancy losses (RPLs) (more than 2)

Cystic Fibrosis
Ashkenazi Jewish Screening
Fragile X Syndrome
Factor V Leiden

There is growing consensus that testing should be performed in at least the following circumstances (these are the same general recommendations for testing for any thrombophilia):
* Venous thrombosis in pregnant women or women taking oral contraceptives.

Testing may also be considered in the following situations:
* Relatives of individuals known to have factor V Leiden. Knowledge that they have factor V Leiden may influence management of pregnancy and may be a factor in decision-making regarding oral contraceptive use.
* Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine fetal growth retardation, or stillbirth. Knowledge of factor V Leiden carrier status may influence management of future pregnancies.

Reasons for Referral to Genetics.ppt

Read more...

Rates of Autism in Fragile X syndrome

Rates of Autism in Fragile X syndrome (FXS)

FXS OVERVIEW
* Fragile X syndrome (FXS), also called Martin-Bell syndrome, is the most common type of inherited intellectual disability
* An inherited condition that is passed down from parents to child, due to a single gene mutation. The abnormal gene is located in the X chromosome.
* About one out of 4,000 males and one out of 8,000 females are born with FXS each year in the United States.
* Mothers with the mutation have 50% chance of passing the gene to their children of both sexes, whereas fathers can only pass it to their daughters.
* Severity of the condition depends on the number of gene repetition.
* patients with FXS experience some combination of symptoms that affect their mental, physical, social, and sensory characteristics. Females with FXS often experience milder symptoms than males.

(http://www.wellness.com/reference/conditions/fragile-x-syndrome-fxs/symptoms-and-causes)

GUILTY GENE
* One in 250 females and 1 in 500 males carries the FMRl gene in a pre-mutation state.
* Located on the long arm of chromosome X, in the q 27.3 region.

CHARACTERISTICS OF FRAGILE X SYNDROME
* FXS has different effects on males and females. Males tend to be more affected than females.
* Intellectual disabilities. ranging from mild to severe. Low IQ score (40-75 for males). Female’s intellectual abilities is considered mild to moderate ,to a relatively normal mental development .
* Physical characteristics:
* elongated face or jaw
* larger ears,
* short stature
* Physical characteristics are usually normal for infants and young children.
* They become noticeable around the 11th year, and become clearly distinct during puberty.
* http://www.wellness.com/reference/conditions/fragile-x-syndrome-fxs/symptoms-and-causes

CHARACTERISTICS OF FRAGILE X SYNDROME
* Social and emotional disabilities:
* Anxiety which leads to avoidance behavior and health issues (heart palpitations, faintness, blushing, and profuse sweating)
* Attention deficit
* Anger issues
* Aggressive behaviors (males)
* Language development: Males and females have different language development
* Difficulty understanding social cues, body language, tone of voice, or facial expressions

CHARACTERISTICS OF AUTISM
* Autism is a behavioral diagnosis with no bio-marker.
* Impaired social interaction
* Impaired communication
* Restricted interests
* Repetitive behaviors

PREVALENCE OF FXS IN AUTISM
* FXS can cause a child to have to have Autism or ASD. However not all children with FXS have Autism
* Between 2% and 16% of all children diagnosed with autism.
* Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism.
* Fragile X syndrome is the most common known single gene cause of autism (http://www.fragilex.org/html/autism_and_fragile_x_syndrome.htm)

DIFFERENCES BETWEEN FXS AND AUTISM
FXS differs from autism in that it can be defined in terms of a specific biomarker: an abnormally expanded sequence of CGG repetitions at the fragile X site at Xq27.3. There is, however, a wide range of individual differences in the length of this triplet expansion, the completeness of the resulting DNA methylation, the levels of transcription and translation into FMR1 mRNA and FMRP, and the modulator effects of polymorphisms in the many genes whose products FMRP regulates.

REFERENCES

* Thomas Johnson, Vanessa A. Checklist Assessments Of FMRl Gene Mutation Phenotypes. Journal of Diversity, Vol, 15, No, 3 Fall 2008
* Belmonte, Matthew K & Bourgeron, Thomas. Fragile X Syndrome and Autism at the Intersection of Genetic and Neural Networks. Nature Neuroscience, Vol 9, No 10, October 2006.
* Feinstein, Carl and Reiss Allan L. Autism: The Point of View from Fragile X Studies. Journal of Autism and Developmental Disorders, Vol. 28, No. 5, 1998
* Brodkin,Edward S. Social Behavior Phenotypes in Fragile X Syndrome, Autism, and the Fmr1
Knockout Mouse: Theoretical Comment on McNaughton et al. (2008). Behavioral Neuroscience /American Psychological Association, 2008, Vol. 122, No. 2, 483–489.
* fragilex.org
* http://www.wellness.com/reference/conditions/fragile-x-syndrome-fxs/symptoms-and-causes


Rates of Autism in Fragile X syndrome (FXS).ppt

Read more...