Genetics and Inheritance: Chromosomes, Disorders, Screening & Birth Defects

DNA

DNA is a nucleic acid containing deoxyribose that stores genetic information; it is mostly in the nucleus, but also in mitochondria and cytoplasm.

DNA nitrogenous bases

Adenine (A) and guanine (G) are purines; cytosine (C) and thymine (T) are pyrimidines.

Gene

A gene is a functional unit of heredity at a specific chromosome location; most genes contain the code to make a specific protein.

Chromosome

Double-stranded DNA containing sections of genes.

Somatic cell chromosomes

46 total: 23 pairs, including 44 autosomes and 2 sex chromosomes.

Sex chromosomes

XX is female; XY is male.

Gametes

Gametes are reproductive cells (oocytes and sperm); they are haploid and contain 23 chromosomes.

Diploid and haploid cells

Diploid cells have two chromosome sets; haploid gametes have one. Fertilization combines the parents' genetic material and restores the diploid number.

Meiosis and fertilization

Gametes are produced by meiosis; each parent contributes half of the offspring's genetic material.

Genotype and phenotype

Genotype is the genetic information inherited at fertilization and may not be visible; phenotype is observable traits such as eye color or blood type.

Mutation

A mutation is an error in DNA duplication. Gamete-cell mutations can be passed to offspring; somatic-cell mutations are not heritable.

Heritable mutations

Deletion, duplication, inversion, insertion, and translocation.

Types of genetic mutations

Deletion removes genetic material; duplication repeats it; inversion reverses a segment; insertion adds genetic material.

Deletion, duplication, inversion, and insertion

A large chromosome segment breaks and reattaches to a different chromosome.

Chromosomal translocation

Alleles are different forms of genes at the same chromosome location; they help determine offspring traits.

Alleles

A trait results from the interaction of several genes.

Polygenic traits

Nondisjunction is incomplete chromosome separation; it can produce an abnormal chromosome number.

Nondisjunction, monosomy, trisomy, and mosaicism

Monosomy: one chromosome copy instead of two. Trisomy: three copies instead of two. Mosaicism: only some cells have an abnormal chromosome number.

Karyotype

A picture of the number and visual appearance of chromosomes.

Mendelian inheritance

A predictable pattern of transmission of single-gene traits.

Homozygous and heterozygous genotypes

Homozygous means identical alleles on each chromosome; heterozygous means two different alleles.

Dominant and recessive alleles

A dominant trait can be expressed with one altered allele; a recessive disorder generally requires two altered alleles.

Autosomal dominant inheritance

One altered allele on an autosome is enough to express the trait.

Autosomal recessive inheritance

Two altered alleles on an autosome are needed to express the disorder.

X-linked inheritance

They are linked to the X chromosome; males have only one X chromosome, so a recessive altered allele on it can be expressed.

Autosomal dominant disorders

Huntington disease, Marfan syndrome, and osteogenesis imperfecta.

Autosomal recessive disorders

Cystic fibrosis, Tay-Sachs disease, and sickle cell disease.

X-linked disorders

Hemophilia and X-linked severe combined immunodeficiency.

Genetic risk assessment

Preconception counseling is ideal; assess family and pregnancy history, screen when risk is identified, then use diagnostic testing if warranted.

Genetic screening and diagnostic testing

Screening estimates the possibility of a condition; diagnostic testing investigates a suspected condition when indicated.

Prenatal screening methods

Maternal quadruple blood screen, ultrasound, and nuchal translucency ultrasound.

Prenatal diagnostic tests

Chorionic villus sampling, amniocentesis, and percutaneous blood sampling.

Newborn screening

Screening performed after birth to identify selected disorders; the slideshow lists it as part of genetic screening and testing.

Sickle cell inheritance pattern

Autosomal recessive. Homozygous individuals have the disease phenotype; heterozygous individuals are carriers.

Sickle cell mutation

A point mutation alters the structure of the beta chain of hemoglobin in red blood cells, producing hemoglobin S (HbS).

Sickled red blood cells

The altered hemoglobin (HbS) is associated with sickled-shaped red blood cells.

Sickle cell clinical manifestations

Jaundice, anemia, pain, organ damage, and infection.

Sickle cell disease severity

The proportion of HbS in the circulation.

Sickle cell diagnostic tests

Genetic screening; hemoglobin electrophoresis; CBC; urinalysis; and liver and kidney function tests.

Sickle cell treatment and prevention

Treat symptoms; prevent infection; avoid temperature extremes; reduce emotional and physical stress; use drugs to promote HbF-containing red cells and treat pain and infection.

Down syndrome chromosome abnormality

Trisomy 21: three copies of chromosome 21, an alteration in autosome number.

Down syndrome causes

It can result from nondisjunction or inherited translocation.

Down syndrome manifestations

Developmental/mental delay, characteristic facial features, cardiac defects, GI malformations, visual and hearing impairment, thyroid dysfunction, and leukemia.

Down syndrome diagnosis

History and physical examination; prenatal nuchal translucency, quadruple screen, assessment for anatomic anomalies, and fetal karyotype.

Down syndrome treatment goals

Promote maximal independence and quality of life through early physical, speech, and occupational therapies and treatment of associated congenital disorders.

Neural tube defects

During embryologic development; they are birth defects involving nervous system tissues.

Types of neural tube defects

Spina bifida and anencephaly.

Spina bifida

Incomplete closure of the vertebrae.

Spina bifida types

Occulta: no protrusion of meninges or spinal cord. Meningocele: meninges protrude. Myelomeningocele: meninges and spinal cord/nerve roots protrude.

Anencephaly

Incomplete closure of the skull with exposure of the brain and meninges.

Neural tube defect diagnosis

Physical examination and prenatal screening with serum alpha-fetoprotein (AFP), amniocentesis, and ultrasound.

Neural tube defect treatment

Anencephaly: supportive care. Spina bifida: surgical correction and supportive care.

Chromosomal abnormalities

Nondisjunction can result in monosomy, trisomy, or mosaicism; translocation moves a chromosome segment to another chromosome.

Single-gene and chromosomal disorders

Single-gene disorders involve altered alleles in a gene; chromosomal disorders involve chromosome number or structure changes.

Family and pregnancy history

It helps identify genetic risk and determine whether screening or diagnostic testing may be appropriate.

Fetal karyotyping

It examines fetal chromosome number and appearance to identify chromosomal abnormalities.

Nuchal translucency screening

Ultrasound; it is a prenatal screening method.

Maternal quadruple screen

The quadruple screen.

Sickle cell disease and Down syndrome

Sickle cell disease is an autosomal recessive single-gene point mutation; Down syndrome is a chromosomal number abnormality (trisomy 21).

Spina bifida and anencephaly

Spina bifida involves incomplete vertebral closure; anencephaly involves incomplete skull closure with exposure of the brain and meninges.