الوراثة والطفرة الجينية

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تحدث الطفرة المتعلقة بجين واحد في أحد أنماط الوراثة الثلاثة، وهي ____ سائد.

مهيمن

نمط الوراثة الثاني هو الوراثة ____.

المتراجعة

الطفرات المرتبطة بالكروموسوم X تُعرف باسم أمراض ____.

مرتبطة

الطفرة في بروتين الفيبريلين تؤدي إلى متلازمة _____ ، التي تؤثر على الأنسجة الضامة.

مارفان Signup and view all the answers

تشمل تأثيرات متلازمة مارفان العيوب في الهيكل العظمي والعينين و _____.

القلب Signup and view all the answers

تحدث ______ نتيجة لاستبدال قاعدة نيوكليوتيد واحدة بأخرى مختلفة.

الطفرة النقطية Signup and view all the answers

في حالة مرض ______ المنجلي، تؤثر الطفرة على سلسلة البيتا جلوبين في الهيموغلوبين.

الأنيميا Signup and view all the answers

تغيير النيوكليوتيد الثلاثي CTC إلى ______ يعد مثالاً على الطفرة النقطية.

CAC Signup and view all the answers

الاستبدال الناتج عن طفرة نقطية يمكن أن يؤدي إلى ______ في منتج البروتين.

استبدال حمض أميني Signup and view all the answers

إذا كانت الطفرة تؤدي إلى تغيير في حمض أميني، فإن هذه الطفرة تعرف باسم ______.

الطفرة غير المعنية Signup and view all the answers

البروتينات الهيكلية الرئيسية تشمل الكولاجين و______ مكونات الغشاء الخلوي الأحمر.

مكونات الهيكل الخلوي Signup and view all the answers

______ هو بروتين موجود في الغشاء الخلوي للكريات الحمراء ويتعلق بالسيربيوسي.

سبكترين Signup and view all the answers

مرض السفيروسي الوراثي يتسبب في تغير شكل الكريات الحمراء بسبب مشاكل في ______.

البروتينات الهيكلية Signup and view all the answers

البروتينات الهيكلية مثل الكولاجين وسبكترين هامة جدًا في ______ الخلايا.

دعم Signup and view all the answers

______ هو نوع من البروتينات التي تكون جزءًا من الغشاء الخلوي للكريات الحمراء.

الكولاجين Signup and view all the answers

نموذج الخلل العصبي النوع 1 يمثل ______% من الحالات.

90 Signup and view all the answers

تتكون الأورام العصبية في النموذج 1 من عقد ______ تظهر من الجلد.

متعددة Signup and view all the answers

الأورام العصبية المرتبطة بالنموذج 1 تتكون من خلايا ______.

شفان Signup and view all the answers

الأورام قد تحدث على طول جذع ______.

العصب Signup and view all the answers

عند حدوث أورام متعددة، قد تتشكل ككتل كبيرة ______.

متعددة الفصوص Signup and view all the answers

تتيح تقنية تفاعل البوليميرات المتسلسل (PCR) ____ لملايين الأضعاف من الحمض النووي أو الحمض النووي الريبي.

تكبير Signup and view all the answers

يمكن استخدام عدد قليل يصل إلى ____ خلايا للتحليل باستخدام تقنية PCR.

1 أو 100 Signup and view all the answers

تساعد تقنية PCR في إجراء تحليل للحمض النووي أو الحمض النووي الريبي من ____ خلايا قليلة.

عينة Signup and view all the answers

تقنية تفاعل البوليميرات المتسلسل تستخدم لتكبير _____ أو RNA.

DNA Signup and view all the answers

تقنية PCR تجعل من الممكن استخدام خلايا قليلة جداً لأغراض _____.

التحليل Signup and view all the answers

إذا كان أحد الوالدين حاملًا لكروموسوم ____ غير طبيعي، فإن الاحتمال يكون مرتفعًا لوجود اضطرابات صبغية.

هيكلي Signup and view all the answers

عند وجود سوء توازن في الجاميتات، فإن النسل سيكون معرضًا لخطر _____.

الاضطرابات الكروموسومية Signup and view all the answers

يمكن ملاحظة الشذوذ الجنيني باستخدام جهاز _____.

الموجات فوق الصوتية Signup and view all the answers

الشذوذات الملاحظة في الفحص بالموجات فوق الصوتية قد تشير إلى وجود _____.

عيوب خلقية Signup and view all the answers

يكون خطر حدوث الاضطرابات الكروموسومية أكبر عندما يكون الوالدان ناقلين لكروموسومات _____.

غير طبيعية Signup and view all the answers

Study Notes

Genetic Diseases

Hereditary disorders are derived from one parent, transmitted through gametes, and are familial.
Congenital diseases are present at birth.
Not all genetic diseases are congenital, and not all congenital diseases are genetic (e.g., congenital syphilis).
Mutations are permanent changes in DNA.
Germ cell mutations are transmitted to offspring, causing inherited diseases.
Somatic cell mutations are not transmitted to offspring but can cause cancers and some congenital malformations.

Types of Mutations

Point mutations result from substituting one nucleotide base with a different base.
This substitution can replace one amino acid in the protein product (e.g., sickle cell anemia).
In sickle cell anemia, the nucleotide triplet CTC (or GAG in mRNA), which encodes glutamic acid, is changed to CAC (or GUG in mRNA), which encodes valine. This is called a missense mutation.
Nonsense mutations change an amino acid codon to a chain termination codon (stop codon), causing rapid degradation of the resultant protein.
A point mutation affecting the codon for glutamine (CAG) creates a stop codon (UAG) if U is substituted for C, resulting in premature termination of the β-globin gene translation, and the short peptide is rapidly degraded. This causes deficiency of β-globin chains and a severe form of anemia called β0-thalassemia.
Frameshift mutations occur when the insertion or deletion of one or two base pairs alters the reading frame of the DNA strand.

Other Types of Mutations

Three-base deletion in the common cystic fibrosis (CF) allele results in synthesis of a protein lacking amino acid 508 (phenylalanine). This is not a frameshift mutation.
A four-base insertion in the hexosaminidase A gene leads to a frameshift mutation, causing Tay-Sachs disease in Ashkenazi Jews.
A single-base deletion at the ABO (glycosyltransferase) locus leads to a frameshift mutation that is responsible for the O allele.
Trinucleotide repeat mutations are characterized by the amplification of a sequence of three nucleotides. For example, in fragile X syndrome, there are 250-4000 repeats of the sequence CGG within the gene called FMR-1. In the normal population, the number of repeats is typically small (29).

Four Types of Genetic Diseases

Those resulting from mutation in a single gene (Mendelian disorders).
Complex disorders involving multiple genes and environmental influences (multifactorial inheritance), e.g., diabetes mellitus.
Chromosomal disorders, arising from structural or numerical alterations in autosomes and sex chromosomes.
Heterogeneous group involving single genes but not following Mendelian inheritance rules.

Diseases Caused by Single Gene Defects

Approximately 1% of all adult and 6-8% of pediatric hospital admissions.
Mutations follow patterns of inheritance: autosomal dominant, autosomal recessive, and X-linked.

Single Gene Mutations May Lead To Multiple Phenotypic Effects

A single gene mutation can lead to multiple phenotypic effects (pleiotropy), e.g., Marfan syndrome. A defect in connective tissue that affects the skeleton, eyes, and cardiovascular systems.
Conversely, multiple mutations can contribute to the same trait (genetic heterogeneity), e.g., retinitis pigmentosa.

Autosomal Dominant Disorders

At least one parent of an affected individual is affected (in heterozygous state).
Both males and females are affected.
Affected individuals marrying unaffected ones have a 50% chance of having an affected child. New mutations can also occur.

Autosomal Recessive Disorders

Affected individuals are homozygous for the mutated gene.
The parents may be carriers (heterozygous) yet unaffected.
Affected siblings have a 25% chance with each birth.
Low frequency of mutation in the population suggests a possible consanguineous marriage.
In heterozygotes, equal amounts of normal and defective enzymes are synthesized, allowing normal enzyme function with a 50% reduction. Clinical symptoms are rarely associated.

X-Linked Disorders

Mostly recessive; only males are affected.
Inherited from heterozygous females to sons, as males are hemizygous for the X chromosome.
Heterozygous females are usually silent carriers.
Affected males do not transmit the disease to their sons, but all daughters are carriers.
Sons of heterozygous mothers have a 50% chance of being affected.
Only few X-linked dominant diseases exist; characterized by transmission to 50% of offspring.

Examples of Autosomal Dominant Disorders

Marfan syndrome
Hypercholesterolemia
Polycystic kidney disease
Hereditary spherocytosis
Familial polyposis coli

Examples of Autosomal Recessive Disorders

Sickle cell anemia
Thalassemia
Glycogen storage disease
Cystic fibrosis
Phenylketonuria
Wilson disease

Examples of X-Linked Disorders

Hemophilia A and B
Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)
Agammaglobulinemia
Duchenne muscular dystrophy

diseases Caused by Structural Proteins

Marfan syndrome, an autosomal dominant disease. Connective tissue protein (fibrillin) has defects. Skeleton, eyes and cardiovascular systems are primarily affected.
Clinical characteristics include:
- Skeletal abnormalities (slender build, long legs and arms, high-arched palate, hyper-extensibility of joints, pectus excavatum or pigeon chest).
- Eye abnormalities (bilateral dislocation or subluxation of the lens, due to weakness of the suspensory ligament, known as ectopia lentis)
- Cardiovascular symptoms (fragmentation of elastic fibers in the aorta (aneurysmal dilation), aortic dissection, aortic valve ring dilation, mitrial and tricuspid valve regurgitation, leading to congestive heart failure).
Death may occur from aortic rupture at any age. Variable expressions of features.

Diseases Caused by Receptor Proteins

Familial hypercholesterolemia. Autosomal dominant disease resulting in elevation of plasma cholesterol levels. Individuals remain asymptomatic until adulthood with the development of xanthomas along tendon sheaths, premature coronary artery disease. Homozygotes are more severely affected with cutaneous xanthomas in childhood and frequently die from myocardial infarction in their teens. Mutation in LDL receptor gene causes the accumulation of LDL cholesterol in the plasma; absence of LDL receptors on the liver impairs transport of IDL to the liver.

Diseases Caused by Mutation in Enzymes

Phenylketonuria (PKU). Inborn error of metabolism; autosomal recessive disorder. Characterized by a severe lack of phenylalanine hydroxylase. This leads to hyperphenylalaninemia, reducing formation of myelin, epinephrine, norepinephrine, myelin, dopamine, thyroxin and melanin in the body. Affected infants display a strong musty or mousy odor. Often accompanied by mental retardation, inability to walk or talk, seizures, decreased skin&hair pigmentation, eczema. Treated with restriction of phenylalanine intake early in life.

Glycogen Storage Disorders (Glycogenosis)

Inherited deficiency of enzymes involved in glycogen synthesis or degradation, leading to excessive glycogen accumulation or abnormal glycogen forms in tissues.
Hepatic forms involve liver enlargement, glycogen storage, and hypoglycemia due to defective glucose production. e.g. von Gierke disease (Glucose-6-phosphatase deficiency).
Myopathic forms involve striated muscle glycogen storage and weakness. Individuals have muscle cramps after exercise and failure of exercise to elevate blood lactate levels. (e.g McArdle disease (Phosphorylase deficiency)).

Diseases Caused By Mutation In Protein That Regulate Cell Growth

Protooncogenes and cancer suppressor genes
Mutations in these genes can lead to tumor formation
About 5% of all cancers are associated with mutations in tumor suppressor genes, which appear in germ cells and can be passed on

Cytogenetic Disorders

Normal chromosome count is 46, a multiple of haploid number (2n=46).
Any number not an exact multiple of n is called aneuploid.
Aneuploidy is frequently caused by non-disjunction during meiosis I or II. Failure of homologous chromosomes or sister chromatids to separate.

Other Disorders

Fragile X Syndrome (X-linked)
Neurofibromatoses (autosomal dominant)
Prader Willi Syndrome (imprinting, deletion in paternal 15q11)
Angleman Syndrome (imprinting, deletion in maternal 15q11)
Mitochondrial diseases

Genetic Analysis Techniques

Karyotyping
Fluorescence in situ hybridization (FISH), and Polymerase chain reaction (PCR)

Genetic Analysis - Prenatal and Postnatal

Prenatal genetic analysis is performed on cells obtained from amniotic fluid, chorionic villi, or umbilical cord blood.
Indications for prenatal testing include maternal age over 35, previous chromosomal abnormality in a child, and identified carriers of genetic disorders.
Postnatal testing uses peripheral blood lymphocytes (e.g. in the case of suspected aneuploidy, sex chromosome abnormalities, or multiple congenital anomalies).
In postnatal analysis, genetic testing can be used for undiagnosed developmental delay, infertility to rule out sex chromosome abnormalities, or multiple spontaneous abortions.

Scientific Breakthroughs

Increased understanding of disease processes.
Potential cures and preventative measures.
Insights on human evolutionary origins.

Gene Therapy

Techniques for genetic alteration of somatic cells.
Involves injecting modified genes targeted for a specific disorder into the patient's blood stream, which then find their way to the defective site and trigger treatment.

Genetic Counseling

Provides valuable information for couples regarding their genetic makeup and associated risks.
Involves studying parental medical records and family history to build a pedigree.

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Description

يتناول هذا الاختبار مفاهيم الطفرات الجينية وأنماط الوراثة المختلفة. تشمل المواضيع الطفرات المرتبطة بالكروموسوم X، ومتلازمة مارفان، وتأثير الطفرات على البروتينات. استعد لتحدي معرفتك حول هذه الموضوعات الحيوية في علم البيولوجيا.